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Published in: Journal of Translational Medicine 1/2009

Open Access 01-12-2009 | Review

Intrinsic and extrinsic factors influencing the clinical course of B-cell chronic lymphocytic leukemia: prognostic markers with pathogenetic relevance

Authors: Michele Dal-Bo, Francesco Bertoni, Francesco Forconi, Antonella Zucchetto, Riccardo Bomben, Roberto Marasca, Silvia Deaglio, Luca Laurenti, Dimitar G Efremov, Gianluca Gaidano, Giovanni Del Poeta, Valter Gattei

Published in: Journal of Translational Medicine | Issue 1/2009

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Abstract

B-cell chronic lymphocytic leukemia (CLL), the most frequent leukemia in the Western world, is characterized by extremely variable clinical courses with survivals ranging from 1 to more than 15 years. The pathogenetic factors playing a key role in defining the biological features of CLL cells, hence eventually influencing the clinical aggressiveness of the disease, are here divided into "intrinsic factors", mainly genomic alterations of CLL cells, and "extrinsic factors", responsible for direct microenvironmental interactions of CLL cells; the latter group includes interactions of CLL cells occurring via the surface B cell receptor (BCR) and dependent to specific molecular features of the BCR itself and/or to the presence of the BCR-associated molecule ZAP-70, or via other non-BCR-dependent interactions, e.g. specific receptor/ligand interactions, such as CD38/CD31 or CD49d/VCAM-1. A putative final model, discussing the pathogenesis and the clinicobiological features of CLL in relationship of these factors, is also provided.
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Literature
1.
go back to reference Moreno C, Montserrat E: New prognostic markers in chronic lymphocytic leukemia. Blood Rev. 2008, 22: 211-219.PubMed Moreno C, Montserrat E: New prognostic markers in chronic lymphocytic leukemia. Blood Rev. 2008, 22: 211-219.PubMed
2.
go back to reference Dohner H, Fischer K, Bentz M, Hansen K, Benner A, Cabot G, Diehl D, Schlenk R, Coy J, Stilgenbauer S: p53 gene deletion predicts for poor survival and non-response to therapy with purine analogs in chronic B-cell leukemias. Blood. 1995, 85: 1580-1589.PubMed Dohner H, Fischer K, Bentz M, Hansen K, Benner A, Cabot G, Diehl D, Schlenk R, Coy J, Stilgenbauer S: p53 gene deletion predicts for poor survival and non-response to therapy with purine analogs in chronic B-cell leukemias. Blood. 1995, 85: 1580-1589.PubMed
3.
go back to reference Damle RN, Wasil T, Fais F, Ghiotto F, Valetto A, Allen SL, Buchbinder A, Budman D, Dittmar K, Kolitz J, Lichtman SM, Schulman P, Vinciguerra VP, Rai KR, Ferrarini M, Chiorazzi N: Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood. 1999, 94: 1840-1847.PubMed Damle RN, Wasil T, Fais F, Ghiotto F, Valetto A, Allen SL, Buchbinder A, Budman D, Dittmar K, Kolitz J, Lichtman SM, Schulman P, Vinciguerra VP, Rai KR, Ferrarini M, Chiorazzi N: Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood. 1999, 94: 1840-1847.PubMed
4.
go back to reference Dohner H, Stilgenbauer S, Benner A, Leupolt E, Krober A, Bullinger L, Dohner K, Bentz M, Lichter P: Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med. 2000, 343: 1910-1916.PubMed Dohner H, Stilgenbauer S, Benner A, Leupolt E, Krober A, Bullinger L, Dohner K, Bentz M, Lichter P: Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med. 2000, 343: 1910-1916.PubMed
5.
go back to reference Orchard JA, Ibbotson RE, Davis Z, Wiestner A, Rosenwald A, Thomas PW, Hamblin TJ, Staudt LM, Oscier DG: ZAP-70 expression and prognosis in chronic lymphocytic leukaemia. Lancet. 2004, 363: 105-111.PubMed Orchard JA, Ibbotson RE, Davis Z, Wiestner A, Rosenwald A, Thomas PW, Hamblin TJ, Staudt LM, Oscier DG: ZAP-70 expression and prognosis in chronic lymphocytic leukaemia. Lancet. 2004, 363: 105-111.PubMed
6.
go back to reference Degan M, Bomben R, Dal Bo M, Zucchetto A, Nanni P, Rupolo M, Steffan A, Attadia V, Ballerini PF, Damiani D, Pucillo C, Del Poeta G, Colombatti A, Gattei V: Analysis of IgV gene mutations in B cell chronic lymphocytic leukaemia according to antigen-driven selection identifies subgroups with different prognosis and usage of the canonical somatic hypermutation machinery. Br J Haematol. 2004, 126: 29-42.PubMed Degan M, Bomben R, Dal Bo M, Zucchetto A, Nanni P, Rupolo M, Steffan A, Attadia V, Ballerini PF, Damiani D, Pucillo C, Del Poeta G, Colombatti A, Gattei V: Analysis of IgV gene mutations in B cell chronic lymphocytic leukaemia according to antigen-driven selection identifies subgroups with different prognosis and usage of the canonical somatic hypermutation machinery. Br J Haematol. 2004, 126: 29-42.PubMed
7.
go back to reference Rassenti LZ, Huynh L, Toy TL, Chen L, Keating MJ, Gribben JG, Neuberg DS, Flinn IW, Rai KR, Byrd JC, Kay NE, Greaves A, Weiss A, Kipps TJ: ZAP-70 compared with immunoglobulin heavy-chain gene mutation status as a predictor of disease progression in chronic lymphocytic leukemia. N Engl J Med. 2004, 351: 893-901.PubMed Rassenti LZ, Huynh L, Toy TL, Chen L, Keating MJ, Gribben JG, Neuberg DS, Flinn IW, Rai KR, Byrd JC, Kay NE, Greaves A, Weiss A, Kipps TJ: ZAP-70 compared with immunoglobulin heavy-chain gene mutation status as a predictor of disease progression in chronic lymphocytic leukemia. N Engl J Med. 2004, 351: 893-901.PubMed
8.
go back to reference Gattei V, Bulian P, Del Principe MI, Zucchetto A, Maurillo L, Buccisano F, Bomben R, Dal-Bo M, Luciano F, Rossi FM, Degan M, Amadori S, Del PG: Relevance of CD49d protein expression as overall survival and progressive disease prognosticator in chronic lymphocytic leukemia. Blood. 2008, 111: 865-873.PubMed Gattei V, Bulian P, Del Principe MI, Zucchetto A, Maurillo L, Buccisano F, Bomben R, Dal-Bo M, Luciano F, Rossi FM, Degan M, Amadori S, Del PG: Relevance of CD49d protein expression as overall survival and progressive disease prognosticator in chronic lymphocytic leukemia. Blood. 2008, 111: 865-873.PubMed
9.
go back to reference Mayr C, Speicher MR, Kofler DM, Buhmann R, Strehl J, Busch R, Hallek M, Wendtner CM: Chromosomal translocations are associated with poor prognosis in chronic lymphocytic leukemia. Blood. 2006, 107: 742-751.PubMed Mayr C, Speicher MR, Kofler DM, Buhmann R, Strehl J, Busch R, Hallek M, Wendtner CM: Chromosomal translocations are associated with poor prognosis in chronic lymphocytic leukemia. Blood. 2006, 107: 742-751.PubMed
10.
go back to reference Haferlach C, Dicker F, Schnittger S, Kern W, Haferlach T: Comprehensive genetic characterization of CLL: a study on 506 cases analysed with chromosome banding analysis, interphase FISH, IgV(H) status and immunophenotyping. Leukemia. 2007, 21: 2442-2451.PubMed Haferlach C, Dicker F, Schnittger S, Kern W, Haferlach T: Comprehensive genetic characterization of CLL: a study on 506 cases analysed with chromosome banding analysis, interphase FISH, IgV(H) status and immunophenotyping. Leukemia. 2007, 21: 2442-2451.PubMed
11.
go back to reference Pfeifer D, Pantic M, Skatulla I, Rawluk J, Kreutz C, Martens UM, Fisch P, Timmer J, Veelken H: Genome-wide analysis of DNA copy number changes and LOH in CLL using high-density SNP arrays. Blood. 2007, 109: 1202-1210.PubMed Pfeifer D, Pantic M, Skatulla I, Rawluk J, Kreutz C, Martens UM, Fisch P, Timmer J, Veelken H: Genome-wide analysis of DNA copy number changes and LOH in CLL using high-density SNP arrays. Blood. 2007, 109: 1202-1210.PubMed
12.
go back to reference Krober A, Seiler T, Benner A, Bullinger L, Bruckle E, Lichter P, Dohner H, Stilgenbauer S: V(H) mutation status, CD38 expression level, genomic aberrations, and survival in chronic lymphocytic leukemia. Blood. 2002, 100: 1410-1416.PubMed Krober A, Seiler T, Benner A, Bullinger L, Bruckle E, Lichter P, Dohner H, Stilgenbauer S: V(H) mutation status, CD38 expression level, genomic aberrations, and survival in chronic lymphocytic leukemia. Blood. 2002, 100: 1410-1416.PubMed
13.
go back to reference Chiorazzi N, Rai KR, Ferrarini M: Chronic Lymphocytic Leukemia. N Engl J Med. 2005, 352: 804-815.PubMed Chiorazzi N, Rai KR, Ferrarini M: Chronic Lymphocytic Leukemia. N Engl J Med. 2005, 352: 804-815.PubMed
14.
go back to reference Nicoloso MS, Kipps TJ, Croce CM, Calin GA: MicroRNAs in the pathogeny of chronic lymphocytic leukaemia. Br J Haematol. 2007, 139: 709-716.PubMed Nicoloso MS, Kipps TJ, Croce CM, Calin GA: MicroRNAs in the pathogeny of chronic lymphocytic leukaemia. Br J Haematol. 2007, 139: 709-716.PubMed
15.
go back to reference Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keating M, Rai K, Rassenti L, Kipps T, Negrini M, Bullrich F, Croce CM: Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA. 2002, 99: 15524-15529.PubMedCentralPubMed Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keating M, Rai K, Rassenti L, Kipps T, Negrini M, Bullrich F, Croce CM: Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA. 2002, 99: 15524-15529.PubMedCentralPubMed
16.
go back to reference Ouillette P, Erba H, Kujawski L, Kaminski M, Shedden K, Malek SN: Integrated genomic profiling of chronic lymphocytic leukemia identifies subtypes of deletion 13q14. Cancer Res. 2008, 68: 1012-1021.PubMed Ouillette P, Erba H, Kujawski L, Kaminski M, Shedden K, Malek SN: Integrated genomic profiling of chronic lymphocytic leukemia identifies subtypes of deletion 13q14. Cancer Res. 2008, 68: 1012-1021.PubMed
17.
go back to reference Valencia-Sanchez MA, Liu J, Hannon GJ, Parker R: Control of translation and mRNA degradation by miRNAs and siRNAs. Genes Dev. 2006, 20: 515-524.PubMed Valencia-Sanchez MA, Liu J, Hannon GJ, Parker R: Control of translation and mRNA degradation by miRNAs and siRNAs. Genes Dev. 2006, 20: 515-524.PubMed
18.
go back to reference Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, Wojcik SE, Aqeilan RI, Zupo S, Dono M, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM: miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA. 2005, 102: 13944-13949.PubMedCentralPubMed Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, Wojcik SE, Aqeilan RI, Zupo S, Dono M, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM: miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA. 2005, 102: 13944-13949.PubMedCentralPubMed
19.
go back to reference Fulci V, Chiaretti S, Goldoni M, Azzalin G, Carucci N, Tavolaro S, Castellano L, Magrelli A, Citarella F, Messina M, Maggio R, Peragine N, Santangelo S, Mauro FR, Landgraf P, Tuschl T, Weir DB, Chien M, Russo JJ, Ju J, Sheridan R, Sander C, Zavolan M, Guarini A, Foa R, Macino G: Quantitative technologies establish a novel microRNA profile of chronic lymphocytic leukemia. Blood. 2007, 109: 4944-4951.PubMed Fulci V, Chiaretti S, Goldoni M, Azzalin G, Carucci N, Tavolaro S, Castellano L, Magrelli A, Citarella F, Messina M, Maggio R, Peragine N, Santangelo S, Mauro FR, Landgraf P, Tuschl T, Weir DB, Chien M, Russo JJ, Ju J, Sheridan R, Sander C, Zavolan M, Guarini A, Foa R, Macino G: Quantitative technologies establish a novel microRNA profile of chronic lymphocytic leukemia. Blood. 2007, 109: 4944-4951.PubMed
20.
go back to reference Calin GA, Cimmino A, Fabbri M, Ferracin M, Wojcik SE, Shimizu M, Taccioli C, Zanesi N, Garzon R, Aqeilan RI, Alder H, Volinia S, Rassenti L, Liu X, Liu CG, Kipps TJ, Negrini M, Croce CM: MiR-15a and miR-16-1 cluster functions in human leukemia. Proc Natl Acad Sci USA. 2008, 105: 5166-5171.PubMedCentralPubMed Calin GA, Cimmino A, Fabbri M, Ferracin M, Wojcik SE, Shimizu M, Taccioli C, Zanesi N, Garzon R, Aqeilan RI, Alder H, Volinia S, Rassenti L, Liu X, Liu CG, Kipps TJ, Negrini M, Croce CM: MiR-15a and miR-16-1 cluster functions in human leukemia. Proc Natl Acad Sci USA. 2008, 105: 5166-5171.PubMedCentralPubMed
21.
go back to reference Buhl AM, Jurlander J, Jorgensen FS, Ottesen AM, Cowland JB, Gjerdrum LM, Hansen BV, Leffers H: Identification of a gene on chromosome 12q22 uniquely overexpressed in chronic lymphocytic leukemia. Blood. 2006, 107: 2904-2911.PubMed Buhl AM, Jurlander J, Jorgensen FS, Ottesen AM, Cowland JB, Gjerdrum LM, Hansen BV, Leffers H: Identification of a gene on chromosome 12q22 uniquely overexpressed in chronic lymphocytic leukemia. Blood. 2006, 107: 2904-2911.PubMed
22.
go back to reference Buhl AM, Novotny GW, Josefsson P, Nielsen JE, Pedersen LB, Geisler C, Rassenti LZ, Kipps TJ, Jurlander J, Leffers H: The CLLU1 expression level is a stable and inherent feature of the chronic lymphocytic leukemia clone. Leukemia. 2009, 23 (6): 1182-6.PubMed Buhl AM, Novotny GW, Josefsson P, Nielsen JE, Pedersen LB, Geisler C, Rassenti LZ, Kipps TJ, Jurlander J, Leffers H: The CLLU1 expression level is a stable and inherent feature of the chronic lymphocytic leukemia clone. Leukemia. 2009, 23 (6): 1182-6.PubMed
23.
go back to reference Josefsson P, Geisler CH, Leffers H, Petersen JH, Andersen MK, Jurlander J, Buhl AM: CLLU1 expression analysis adds prognostic information to risk prediction in chronic lymphocytic leukemia. Blood. 2007, 109: 4973-4979.PubMed Josefsson P, Geisler CH, Leffers H, Petersen JH, Andersen MK, Jurlander J, Buhl AM: CLLU1 expression analysis adds prognostic information to risk prediction in chronic lymphocytic leukemia. Blood. 2007, 109: 4973-4979.PubMed
24.
go back to reference Austen B, Powell JE, Alvi A, Edwards I, Hooper L, Starczynski J, Taylor AM, Fegan C, Moss P, Stankovic T: Mutations in the ATM gene lead to impaired overall and treatment-free survival that is independent of IGVH mutation status in patients with B-CLL. Blood. 2005, 106: 3175-3182.PubMed Austen B, Powell JE, Alvi A, Edwards I, Hooper L, Starczynski J, Taylor AM, Fegan C, Moss P, Stankovic T: Mutations in the ATM gene lead to impaired overall and treatment-free survival that is independent of IGVH mutation status in patients with B-CLL. Blood. 2005, 106: 3175-3182.PubMed
25.
go back to reference Oscier DG, Gardiner AC, Mould SJ, Glide S, Davis ZA, Ibbotson RE, Corcoran MM, Chapman RM, Thomas PW, Copplestone JA, Orchard JA, Hamblin TJ: Multivariate analysis of prognostic factors in CLL: clinical stage, IGVH gene mutational status, and loss or mutation of the p53 gene are independent prognostic factors. Blood. 2002, 100: 1177-1184.PubMed Oscier DG, Gardiner AC, Mould SJ, Glide S, Davis ZA, Ibbotson RE, Corcoran MM, Chapman RM, Thomas PW, Copplestone JA, Orchard JA, Hamblin TJ: Multivariate analysis of prognostic factors in CLL: clinical stage, IGVH gene mutational status, and loss or mutation of the p53 gene are independent prognostic factors. Blood. 2002, 100: 1177-1184.PubMed
26.
go back to reference Byrd JC, Gribben JG, Peterson BL, Grever MR, Lozanski G, Lucas DM, Lampson B, Larson RA, Caligiuri MA, Heerema NA: Select high-risk genetic features predict earlier progression following chemoimmunotherapy with fludarabine and rituximab in chronic lymphocytic leukemia: justification for risk-adapted therapy. J Clin Oncol. 2006, 24: 437-443.PubMed Byrd JC, Gribben JG, Peterson BL, Grever MR, Lozanski G, Lucas DM, Lampson B, Larson RA, Caligiuri MA, Heerema NA: Select high-risk genetic features predict earlier progression following chemoimmunotherapy with fludarabine and rituximab in chronic lymphocytic leukemia: justification for risk-adapted therapy. J Clin Oncol. 2006, 24: 437-443.PubMed
27.
go back to reference Krober A, Bloehdorn J, Hafner S, Buhler A, Seiler T, Kienle D, Winkler D, Bangerter M, Schlenk RF, Benner A, Lichter P, Dohner H, Stilgenbauer S: Additional genetic high-risk features such as 11q deletion, 17p deletion, and V3-21 usage characterize discordance of ZAP-70 and VH mutation status in chronic lymphocytic leukemia. J Clin Oncol. 2006, 24: 969-975.PubMed Krober A, Bloehdorn J, Hafner S, Buhler A, Seiler T, Kienle D, Winkler D, Bangerter M, Schlenk RF, Benner A, Lichter P, Dohner H, Stilgenbauer S: Additional genetic high-risk features such as 11q deletion, 17p deletion, and V3-21 usage characterize discordance of ZAP-70 and VH mutation status in chronic lymphocytic leukemia. J Clin Oncol. 2006, 24: 969-975.PubMed
28.
go back to reference Austen B, Skowronska A, Baker C, Powell JE, Gardiner A, Oscier D, Majid A, Dyer M, Siebert R, Taylor AM, Moss PA, Stankovic T: Mutation status of the residual ATM allele is an important determinant of the cellular response to chemotherapy and survival in patients with chronic lymphocytic leukemia containing an 11q deletion. J Clin Oncol. 2007, 25: 5448-5457.PubMed Austen B, Skowronska A, Baker C, Powell JE, Gardiner A, Oscier D, Majid A, Dyer M, Siebert R, Taylor AM, Moss PA, Stankovic T: Mutation status of the residual ATM allele is an important determinant of the cellular response to chemotherapy and survival in patients with chronic lymphocytic leukemia containing an 11q deletion. J Clin Oncol. 2007, 25: 5448-5457.PubMed
29.
go back to reference Kalla C, Scheuermann MO, Kube I, Schlotter M, Mertens D, Dohner H, Stilgenbauer S, Lichter P: Analysis of 11q22-q23 deletion target genes in B-cell chronic lymphocytic leukaemia: evidence for a pathogenic role of NPAT, CUL5, and PPP2R1B. Eur J Cancer. 2007, 43: 1328-1335.PubMed Kalla C, Scheuermann MO, Kube I, Schlotter M, Mertens D, Dohner H, Stilgenbauer S, Lichter P: Analysis of 11q22-q23 deletion target genes in B-cell chronic lymphocytic leukaemia: evidence for a pathogenic role of NPAT, CUL5, and PPP2R1B. Eur J Cancer. 2007, 43: 1328-1335.PubMed
30.
go back to reference Seiler T, Dohner H, Stilgenbauer S: Risk stratification in chronic lymphocytic leukemia. Semin Oncol. 2006, 33: 186-194.PubMed Seiler T, Dohner H, Stilgenbauer S: Risk stratification in chronic lymphocytic leukemia. Semin Oncol. 2006, 33: 186-194.PubMed
31.
go back to reference Harris SL, Levine AJ: The p53 pathway: positive and negative feedback loops. Oncogene. 2005, 24: 2899-2908.PubMed Harris SL, Levine AJ: The p53 pathway: positive and negative feedback loops. Oncogene. 2005, 24: 2899-2908.PubMed
32.
go back to reference Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, Kong N, Kammlott U, Lukacs C, Klein C, Fotouhi N, Liu EA: In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science. 2004, 303: 844-848.PubMed Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, Kong N, Kammlott U, Lukacs C, Klein C, Fotouhi N, Liu EA: In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science. 2004, 303: 844-848.PubMed
33.
go back to reference Michael D, Oren M: The p53 and Mdm2 families in cancer. Curr Opin Genet Dev. 2002, 12: 53-59.PubMed Michael D, Oren M: The p53 and Mdm2 families in cancer. Curr Opin Genet Dev. 2002, 12: 53-59.PubMed
34.
go back to reference Michael D, Oren M: The p53-Mdm2 module and the ubiquitin system. Semin Cancer Biol. 2003, 13: 49-58.PubMed Michael D, Oren M: The p53-Mdm2 module and the ubiquitin system. Semin Cancer Biol. 2003, 13: 49-58.PubMed
35.
go back to reference Vassilev LT: MDM2 inhibitors for cancer therapy. Trends Mol Med. 2007, 13: 23-31.PubMed Vassilev LT: MDM2 inhibitors for cancer therapy. Trends Mol Med. 2007, 13: 23-31.PubMed
36.
go back to reference Stommel JM, Wahl GM: Accelerated MDM2 auto-degradation induced by DNA-damage kinases is required for p53 activation. EMBO J. 2004, 23: 1547-1556.PubMedCentralPubMed Stommel JM, Wahl GM: Accelerated MDM2 auto-degradation induced by DNA-damage kinases is required for p53 activation. EMBO J. 2004, 23: 1547-1556.PubMedCentralPubMed
37.
go back to reference Secchiero P, Barbarotto E, Tiribelli M, Zerbinati C, di Iasio MG, Gonelli A, Cavazzini F, Campioni D, Fanin R, Cuneo A, Zauli G: Functional integrity of the p53-mediated apoptotic pathway induced by the nongenotoxic agent nutlin-3 in B-cell chronic lymphocytic leukemia (B-CLL). Blood. 2006, 107: 4122-4129.PubMed Secchiero P, Barbarotto E, Tiribelli M, Zerbinati C, di Iasio MG, Gonelli A, Cavazzini F, Campioni D, Fanin R, Cuneo A, Zauli G: Functional integrity of the p53-mediated apoptotic pathway induced by the nongenotoxic agent nutlin-3 in B-cell chronic lymphocytic leukemia (B-CLL). Blood. 2006, 107: 4122-4129.PubMed
38.
go back to reference Shanafelt TD, Witzig TE, Fink SR, Jenkins RB, Paternoster SF, Smoley SA, Stockero KJ, Nast DM, Flynn HC, Tschumper RC, Geyer S, Zent CS, Call TG, Jelinek DF, Kay NE, Dewald GW: Prospective evaluation of clonal evolution during long-term follow-up of patients with untreated early-stage chronic lymphocytic leukemia. J Clin Oncol. 2006, 24: 4634-4641.PubMed Shanafelt TD, Witzig TE, Fink SR, Jenkins RB, Paternoster SF, Smoley SA, Stockero KJ, Nast DM, Flynn HC, Tschumper RC, Geyer S, Zent CS, Call TG, Jelinek DF, Kay NE, Dewald GW: Prospective evaluation of clonal evolution during long-term follow-up of patients with untreated early-stage chronic lymphocytic leukemia. J Clin Oncol. 2006, 24: 4634-4641.PubMed
39.
go back to reference Stilgenbauer S, Sander S, Bullinger L, Benner A, Leupolt E, Winkler D, Krober A, Kienle D, Lichter P, Dohner H: Clonal evolution in chronic lymphocytic leukemia: acquisition of high-risk genomic aberrations associated with unmutated VH, resistance to therapy, and short survival. Haematologica. 2007, 92: 1242-1245.PubMed Stilgenbauer S, Sander S, Bullinger L, Benner A, Leupolt E, Winkler D, Krober A, Kienle D, Lichter P, Dohner H: Clonal evolution in chronic lymphocytic leukemia: acquisition of high-risk genomic aberrations associated with unmutated VH, resistance to therapy, and short survival. Haematologica. 2007, 92: 1242-1245.PubMed
40.
go back to reference Shanafelt TD, Hanson C, Dewald GW, Witzig TE, Laplant B, Abrahamzon J, Jelinek DF, Kay NE: Karyotype evolution on fluorescent in situ hybridization analysis is associated with short survival in patients with chronic lymphocytic leukemia and is related to CD49d expression. J Clin Oncol. 2008, 26: e5-e6.PubMedCentralPubMed Shanafelt TD, Hanson C, Dewald GW, Witzig TE, Laplant B, Abrahamzon J, Jelinek DF, Kay NE: Karyotype evolution on fluorescent in situ hybridization analysis is associated with short survival in patients with chronic lymphocytic leukemia and is related to CD49d expression. J Clin Oncol. 2008, 26: e5-e6.PubMedCentralPubMed
41.
go back to reference Lozanski G, Heerema NA, Flinn IW, Smith L, Harbison J, Webb J, Moran M, Lucas M, Lin T, Hackbarth ML, Proffitt JH, Lucas D, Grever MR, Byrd JC: Alemtuzumab is an effective therapy for chronic lymphocytic leukemia with p53 mutations and deletions. Blood. 2004, 103: 3278-3281.PubMed Lozanski G, Heerema NA, Flinn IW, Smith L, Harbison J, Webb J, Moran M, Lucas M, Lin T, Hackbarth ML, Proffitt JH, Lucas D, Grever MR, Byrd JC: Alemtuzumab is an effective therapy for chronic lymphocytic leukemia with p53 mutations and deletions. Blood. 2004, 103: 3278-3281.PubMed
42.
go back to reference Rossi D, Cerri M, Deambrogi C, Sozzi E, Cresta S, Rasi S, De PL, Spina V, Gattei V, Capello D, Forconi F, Lauria F, Gaidano G: The prognostic value of TP53 mutations in chronic lymphocytic leukemia is independent of Del17p13: implications for overall survival and chemorefractoriness. Clin Cancer Res. 2009, 15: 995-1004.PubMed Rossi D, Cerri M, Deambrogi C, Sozzi E, Cresta S, Rasi S, De PL, Spina V, Gattei V, Capello D, Forconi F, Lauria F, Gaidano G: The prognostic value of TP53 mutations in chronic lymphocytic leukemia is independent of Del17p13: implications for overall survival and chemorefractoriness. Clin Cancer Res. 2009, 15: 995-1004.PubMed
43.
go back to reference Pettitt AR, Sherrington PD, Stewart G, Cawley JC, Taylor AM, Stankovic T: p53 dysfunction in B-cell chronic lymphocytic leukemia: inactivation of ATM as an alternative to TP53 mutation. Blood. 2001, 98: 814-822.PubMed Pettitt AR, Sherrington PD, Stewart G, Cawley JC, Taylor AM, Stankovic T: p53 dysfunction in B-cell chronic lymphocytic leukemia: inactivation of ATM as an alternative to TP53 mutation. Blood. 2001, 98: 814-822.PubMed
44.
go back to reference Valganon M, Giraldo P, Agirre X, Larrayoz MJ, Rubio-Martinez A, Rubio-Felix D, Calasanz MJ, Odero MD: p53 Aberrations do not predict individual response to fludarabine in patients with B-cell chronic lymphocytic leukaemia in advanced stages Rai III/IV. Br J Haematol. 2005, 129: 53-59.PubMed Valganon M, Giraldo P, Agirre X, Larrayoz MJ, Rubio-Martinez A, Rubio-Felix D, Calasanz MJ, Odero MD: p53 Aberrations do not predict individual response to fludarabine in patients with B-cell chronic lymphocytic leukaemia in advanced stages Rai III/IV. Br J Haematol. 2005, 129: 53-59.PubMed
45.
go back to reference Sturm I, Bosanquet AG, Hummel M, Dorken B, Daniel PT: In B-CLL, the codon 72 polymorphic variants of p53 are not related to drug resistance and disease prognosis. BMC Cancer. 2005, 5: 105-PubMedCentralPubMed Sturm I, Bosanquet AG, Hummel M, Dorken B, Daniel PT: In B-CLL, the codon 72 polymorphic variants of p53 are not related to drug resistance and disease prognosis. BMC Cancer. 2005, 5: 105-PubMedCentralPubMed
46.
go back to reference Gryshchenko I, Hofbauer S, Stoecher M, Daniel PT, Steurer M, Gaiger A, Eigenberger K, Greil R, Tinhofer I: MDM2 SNP309 is associated with poor outcome in B-cell chronic lymphocytic leukemia. J Clin Oncol. 2008, 26: 2252-2257.PubMed Gryshchenko I, Hofbauer S, Stoecher M, Daniel PT, Steurer M, Gaiger A, Eigenberger K, Greil R, Tinhofer I: MDM2 SNP309 is associated with poor outcome in B-cell chronic lymphocytic leukemia. J Clin Oncol. 2008, 26: 2252-2257.PubMed
47.
go back to reference Dighiero G, Hamblin TJ: Chronic lymphocytic leukaemia. Lancet. 2008, 371: 1017-1029.PubMed Dighiero G, Hamblin TJ: Chronic lymphocytic leukaemia. Lancet. 2008, 371: 1017-1029.PubMed
48.
go back to reference Grever MR, Lucas DM, Johnson AJ, Byrd JC: Novel agents and strategies for treatment of p53-defective chronic lymphocytic leukemia. Best Pract Res Clin Haematol. 2007, 20: 545-556.PubMed Grever MR, Lucas DM, Johnson AJ, Byrd JC: Novel agents and strategies for treatment of p53-defective chronic lymphocytic leukemia. Best Pract Res Clin Haematol. 2007, 20: 545-556.PubMed
49.
go back to reference Zenz T, Dohner H, Stilgenbauer S: Genetics and risk-stratified approach to therapy in chronic lymphocytic leukemia. Best Pract Res Clin Haematol. 2007, 20: 439-453.PubMed Zenz T, Dohner H, Stilgenbauer S: Genetics and risk-stratified approach to therapy in chronic lymphocytic leukemia. Best Pract Res Clin Haematol. 2007, 20: 439-453.PubMed
50.
go back to reference Dicker F, Schnittger S, Haferlach T, Kern W, Schoch C: Immunostimulatory oligonucleotide-induced metaphase cytogenetics detect chromosomal aberrations in 80% of CLL patients: A study of 132 CLL cases with correlation to FISH, IgVH status, and CD38 expression. Blood. 2006, 108: 3152-3160.PubMed Dicker F, Schnittger S, Haferlach T, Kern W, Schoch C: Immunostimulatory oligonucleotide-induced metaphase cytogenetics detect chromosomal aberrations in 80% of CLL patients: A study of 132 CLL cases with correlation to FISH, IgVH status, and CD38 expression. Blood. 2006, 108: 3152-3160.PubMed
51.
go back to reference Bentz M, Huck K, du MS, Joos S, Werner CA, Fischer K, Dohner H, Lichter P: Comparative genomic hybridization in chronic B-cell leukemias shows a high incidence of chromosomal gains and losses. Blood. 1995, 85: 3610-3618.PubMed Bentz M, Huck K, du MS, Joos S, Werner CA, Fischer K, Dohner H, Lichter P: Comparative genomic hybridization in chronic B-cell leukemias shows a high incidence of chromosomal gains and losses. Blood. 1995, 85: 3610-3618.PubMed
52.
go back to reference Novak U, Oppliger LE, Hager J, Muhlematter D, Jotterand M, Besse C, Leupin N, Ratschiller D, Papp J, Kearsey G, Aebi S, Graber H, Jaggi R, Luthi JM, Meyer-Monard S, Lathrop M, Tobler A, Fey MF: A high-resolution allelotype of B-cell chronic lymphocytic leukemia (B-CLL). Blood. 2002, 100: 1787-1794.PubMed Novak U, Oppliger LE, Hager J, Muhlematter D, Jotterand M, Besse C, Leupin N, Ratschiller D, Papp J, Kearsey G, Aebi S, Graber H, Jaggi R, Luthi JM, Meyer-Monard S, Lathrop M, Tobler A, Fey MF: A high-resolution allelotype of B-cell chronic lymphocytic leukemia (B-CLL). Blood. 2002, 100: 1787-1794.PubMed
53.
go back to reference Ottaggio L, Viaggi S, Zunino A, Zupo S, Rossi E, Spriano M, Abbondandolo A, Ferrarini M: Chromosome aberrations evaluated by comparative genomic hybridization in B-cell chronic lymphocytic leukemia: correlation with CD38 expression. Haematologica. 2003, 88: 769-777.PubMed Ottaggio L, Viaggi S, Zunino A, Zupo S, Rossi E, Spriano M, Abbondandolo A, Ferrarini M: Chromosome aberrations evaluated by comparative genomic hybridization in B-cell chronic lymphocytic leukemia: correlation with CD38 expression. Haematologica. 2003, 88: 769-777.PubMed
54.
go back to reference Forconi F, Rinaldi A, Kwee I, Sozzi E, Raspadori D, Rancoita PM, Scandurra M, Rossi D, Deambrogi C, Capello D, Zucca E, Marconi D, Bomben R, Gattei V, Lauria F, Gaidano G, Bertoni F: Genome-wide DNA analysis identifies recurrent imbalances predicting outcome in chronic lymphocytic leukaemia with 17p deletion. Br J Haematol. 2008, 143: 532-536.PubMed Forconi F, Rinaldi A, Kwee I, Sozzi E, Raspadori D, Rancoita PM, Scandurra M, Rossi D, Deambrogi C, Capello D, Zucca E, Marconi D, Bomben R, Gattei V, Lauria F, Gaidano G, Bertoni F: Genome-wide DNA analysis identifies recurrent imbalances predicting outcome in chronic lymphocytic leukaemia with 17p deletion. Br J Haematol. 2008, 143: 532-536.PubMed
55.
go back to reference Bechter OE, Eisterer W, Pall G, Hilbe W, Kuhr T, Thaler J: Telomere length and telomerase activity predict survival in patients with B cell chronic lymphocytic leukemia. Cancer Res. 1998, 58: 4918-4922.PubMed Bechter OE, Eisterer W, Pall G, Hilbe W, Kuhr T, Thaler J: Telomere length and telomerase activity predict survival in patients with B cell chronic lymphocytic leukemia. Cancer Res. 1998, 58: 4918-4922.PubMed
56.
go back to reference Damle RN, Batliwalla FM, Ghiotto F, Valetto A, Albesiano E, Sison C, Allen SL, Kolitz J, Vinciguerra VP, Kudalkar P, Wasil T, Rai KR, Ferrarini M, Gregersen PK, Chiorazzi N: Telomere length and telomerase activity delineate distinctive replicative features of the B-CLL subgroups defined by immunoglobulin V gene mutations. Blood. 2004, 103: 375-382.PubMed Damle RN, Batliwalla FM, Ghiotto F, Valetto A, Albesiano E, Sison C, Allen SL, Kolitz J, Vinciguerra VP, Kudalkar P, Wasil T, Rai KR, Ferrarini M, Gregersen PK, Chiorazzi N: Telomere length and telomerase activity delineate distinctive replicative features of the B-CLL subgroups defined by immunoglobulin V gene mutations. Blood. 2004, 103: 375-382.PubMed
57.
go back to reference Grabowski P, Hultdin M, Karlsson K, Tobin G, Aleskog A, Thunberg U, Laurell A, Sundstrom C, Rosenquist R, Roos G: Telomere length as a prognostic parameter in chronic lymphocytic leukemia with special reference to VH gene mutation status. Blood. 2005, 105: 4807-4812.PubMed Grabowski P, Hultdin M, Karlsson K, Tobin G, Aleskog A, Thunberg U, Laurell A, Sundstrom C, Rosenquist R, Roos G: Telomere length as a prognostic parameter in chronic lymphocytic leukemia with special reference to VH gene mutation status. Blood. 2005, 105: 4807-4812.PubMed
58.
go back to reference Roos G, Krober A, Grabowski P, Kienle D, Buhler A, Dohner H, Rosenquist R, Stilgenbauer S: Short telomeres are associated with genetic complexity, high-risk genomic aberrations, and short survival in chronic lymphocytic leukemia. Blood. 2008, 111: 2246-2252.PubMed Roos G, Krober A, Grabowski P, Kienle D, Buhler A, Dohner H, Rosenquist R, Stilgenbauer S: Short telomeres are associated with genetic complexity, high-risk genomic aberrations, and short survival in chronic lymphocytic leukemia. Blood. 2008, 111: 2246-2252.PubMed
59.
go back to reference Terrin L, Trentin L, Degan M, Corradini I, Bertorelle R, Carli P, Maschio N, Bo MD, Noventa F, Gattei V, Semenzato G, De RA: Telomerase expression in B-cell chronic lymphocytic leukemia predicts survival and delineates subgroups of patients with the same igVH mutation status and different outcome. Leukemia. 2007, 21: 965-972.PubMed Terrin L, Trentin L, Degan M, Corradini I, Bertorelle R, Carli P, Maschio N, Bo MD, Noventa F, Gattei V, Semenzato G, De RA: Telomerase expression in B-cell chronic lymphocytic leukemia predicts survival and delineates subgroups of patients with the same igVH mutation status and different outcome. Leukemia. 2007, 21: 965-972.PubMed
60.
go back to reference Weng NP, Granger L, Hodes RJ: Telomere lengthening and telomerase activation during human B cell differentiation. Proc Natl Acad Sci USA. 1997, 94: 10827-10832.PubMedCentralPubMed Weng NP, Granger L, Hodes RJ: Telomere lengthening and telomerase activation during human B cell differentiation. Proc Natl Acad Sci USA. 1997, 94: 10827-10832.PubMedCentralPubMed
61.
go back to reference Ladetto M, Compagno M, Ricca I, Pagano M, Rocci A, Astolfi M, Drandi D, di Celle PF, Dell'Aquila M, Mantoan B, Vallet S, Pagliano G, De MF, Francese R, Santo L, Cuttica A, Marinone C, Boccadoro M, Tarella C: Telomere length correlates with histopathogenesis according to the germinal center in mature B-cell lymphoproliferative disorders. Blood. 2004, 103: 4644-4649.PubMed Ladetto M, Compagno M, Ricca I, Pagano M, Rocci A, Astolfi M, Drandi D, di Celle PF, Dell'Aquila M, Mantoan B, Vallet S, Pagliano G, De MF, Francese R, Santo L, Cuttica A, Marinone C, Boccadoro M, Tarella C: Telomere length correlates with histopathogenesis according to the germinal center in mature B-cell lymphoproliferative disorders. Blood. 2004, 103: 4644-4649.PubMed
62.
go back to reference Klein U, Tu Y, Stolovitzky GA, Mattioli M, Cattoretti G, Husson H, Freedman A, Inghirami G, Cro L, Baldini L, Neri A, Califano A, Dalla-Favera R: Gene expression profiling of B cell chronic lymphocytic leukemia reveals a homogeneous phenotype related to memory B cells. J Exp Med. 2001, 194: 1625-1638.PubMedCentralPubMed Klein U, Tu Y, Stolovitzky GA, Mattioli M, Cattoretti G, Husson H, Freedman A, Inghirami G, Cro L, Baldini L, Neri A, Califano A, Dalla-Favera R: Gene expression profiling of B cell chronic lymphocytic leukemia reveals a homogeneous phenotype related to memory B cells. J Exp Med. 2001, 194: 1625-1638.PubMedCentralPubMed
63.
go back to reference Rosenwald A, Alizadeh AA, Widhopf G, Simon R, Davis RE, Yu X, Yang L, Pickeral OK, Rassenti LZ, Powell J, Botstein D, Byrd JC, Grever MR, Cheson BD, Chiorazzi N, Wilson WH, Kipps TJ, Brown PO, Staudt LM: Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia. J Exp Med. 2001, 194: 1639-1647.PubMedCentralPubMed Rosenwald A, Alizadeh AA, Widhopf G, Simon R, Davis RE, Yu X, Yang L, Pickeral OK, Rassenti LZ, Powell J, Botstein D, Byrd JC, Grever MR, Cheson BD, Chiorazzi N, Wilson WH, Kipps TJ, Brown PO, Staudt LM: Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia. J Exp Med. 2001, 194: 1639-1647.PubMedCentralPubMed
64.
go back to reference Klein U, la-Favera R: New insights into the phenotype and cell derivation of B cell chronic lymphocytic leukemia. Curr Top Microbiol Immunol. 2005, 294: 31-49.PubMed Klein U, la-Favera R: New insights into the phenotype and cell derivation of B cell chronic lymphocytic leukemia. Curr Top Microbiol Immunol. 2005, 294: 31-49.PubMed
65.
go back to reference Caligaris-Cappio F, Ghia P: The normal counterpart to the chronic lymphocytic leukemia B cell. Best Pract Res Clin Haematol. 2007, 20: 385-397.PubMed Caligaris-Cappio F, Ghia P: The normal counterpart to the chronic lymphocytic leukemia B cell. Best Pract Res Clin Haematol. 2007, 20: 385-397.PubMed
66.
go back to reference Odegard VH, Schatz DG: Targeting of somatic hypermutation. Nat Rev Immunol. 2006, 6: 573-583.PubMed Odegard VH, Schatz DG: Targeting of somatic hypermutation. Nat Rev Immunol. 2006, 6: 573-583.PubMed
67.
go back to reference Moreau EJ, Matutes E, A'Hern RP, Morilla AM, Morilla RM, Owusu-Ankomah KA, Seon BK, Catovsky D: Improvement of the chronic lymphocytic leukemia scoring system with the monoclonal antibody SN8 (CD79b). Am J Clin Pathol. 1997, 108: 378-382.PubMed Moreau EJ, Matutes E, A'Hern RP, Morilla AM, Morilla RM, Owusu-Ankomah KA, Seon BK, Catovsky D: Improvement of the chronic lymphocytic leukemia scoring system with the monoclonal antibody SN8 (CD79b). Am J Clin Pathol. 1997, 108: 378-382.PubMed
68.
go back to reference Potter KN, Mockridge CI, Neville L, Wheatley I, Schenk M, Orchard J, Duncombe AS, Packham G, Stevenson FK: Structural and functional features of the B-cell receptor in IgG-positive chronic lymphocytic leukemia. Clin Cancer Res. 2006, 12: 1672-1679.PubMed Potter KN, Mockridge CI, Neville L, Wheatley I, Schenk M, Orchard J, Duncombe AS, Packham G, Stevenson FK: Structural and functional features of the B-cell receptor in IgG-positive chronic lymphocytic leukemia. Clin Cancer Res. 2006, 12: 1672-1679.PubMed
69.
go back to reference Schroeder HW, Dighiero G: The pathogenesis of chronic lymphocytic leukemia: analysis of the antibody repertoire. Immunol Today. 1994, 15: 288-294.PubMed Schroeder HW, Dighiero G: The pathogenesis of chronic lymphocytic leukemia: analysis of the antibody repertoire. Immunol Today. 1994, 15: 288-294.PubMed
70.
go back to reference Oscier DG, Thompsett A, Zhu D, Stevenson FK: Differential rates of somatic hypermutation in V(H) genes among subsets of chronic lymphocytic leukemia defined by chromosomal abnormalities. Blood. 1997, 89: 4153-4160.PubMed Oscier DG, Thompsett A, Zhu D, Stevenson FK: Differential rates of somatic hypermutation in V(H) genes among subsets of chronic lymphocytic leukemia defined by chromosomal abnormalities. Blood. 1997, 89: 4153-4160.PubMed
71.
go back to reference Fais F, Ghiotto F, Hashimoto S, Sellars B, Valetto A, Allen SL, Schulman P, Vinciguerra VP, Rai K, Rassenti LZ, Kipps TJ, Dighiero G, Schroeder HW, Ferrarini M, Chiorazzi N: Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors. J Clin Invest. 1998, 102: 1515-1525.PubMedCentralPubMed Fais F, Ghiotto F, Hashimoto S, Sellars B, Valetto A, Allen SL, Schulman P, Vinciguerra VP, Rai K, Rassenti LZ, Kipps TJ, Dighiero G, Schroeder HW, Ferrarini M, Chiorazzi N: Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors. J Clin Invest. 1998, 102: 1515-1525.PubMedCentralPubMed
72.
go back to reference Chang B, Casali P: The CDR1 sequences of a major proportion of human germline Ig VH genes are inherently susceptible to amino acid replacement. Immunol Today. 1994, 15: 367-373.PubMed Chang B, Casali P: The CDR1 sequences of a major proportion of human germline Ig VH genes are inherently susceptible to amino acid replacement. Immunol Today. 1994, 15: 367-373.PubMed
73.
go back to reference Chang B, Casali P: A sequence analysis of human germline Ig VH and VL genes. The CDR1s of a major proportion of VH, but not VL, genes display a high inherent susceptibility to amino acid replacement. Ann N Y Acad Sci. 1995, 764: 170-179.PubMed Chang B, Casali P: A sequence analysis of human germline Ig VH and VL genes. The CDR1s of a major proportion of VH, but not VL, genes display a high inherent susceptibility to amino acid replacement. Ann N Y Acad Sci. 1995, 764: 170-179.PubMed
74.
go back to reference Lossos IS, Tibshirani R, Narasimhan B, Levy R: The inference of antigen selection on Ig genes. J Immunol. 2000, 165: 5122-5126.PubMed Lossos IS, Tibshirani R, Narasimhan B, Levy R: The inference of antigen selection on Ig genes. J Immunol. 2000, 165: 5122-5126.PubMed
75.
go back to reference Keating MJ, Chiorazzi N, Messmer B, Damle RN, Allen SL, Rai KR, Ferrarini M, Kipps TJ: Biology and treatment of chronic lymphocytic leukemia. Hematology (Am.Soc Hematol.Educ Program). 2003, 153-175. Keating MJ, Chiorazzi N, Messmer B, Damle RN, Allen SL, Rai KR, Ferrarini M, Kipps TJ: Biology and treatment of chronic lymphocytic leukemia. Hematology (Am.Soc Hematol.Educ Program). 2003, 153-175.
76.
go back to reference Bomben R, Dal Bo M, Zucchetto A, Zaina E, Nanni P, Sonego P, Del Poeta G, Degan M, Gattei V: Mutational status of IgV(H) genes in B-cell chronic lymphocytic leukemia and prognosis: percent mutations or antigen-driven selection?. Leukemia. 2005, 19: 1490-1492.PubMed Bomben R, Dal Bo M, Zucchetto A, Zaina E, Nanni P, Sonego P, Del Poeta G, Degan M, Gattei V: Mutational status of IgV(H) genes in B-cell chronic lymphocytic leukemia and prognosis: percent mutations or antigen-driven selection?. Leukemia. 2005, 19: 1490-1492.PubMed
77.
go back to reference Hamblin TJ, Davis Z, Gardiner A, Oscier DG, Stevenson FK: Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood. 1999, 94: 1848-1854.PubMed Hamblin TJ, Davis Z, Gardiner A, Oscier DG, Stevenson FK: Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood. 1999, 94: 1848-1854.PubMed
78.
go back to reference Dreger P, Stilgenbauer S, Benner A, Ritgen M, Krober A, Kneba M, Schmitz N, Dohner H: The prognostic impact of autologous stem cell transplantation in patients with chronic lymphocytic leukemia: a risk-matched analysis based on the VH gene mutational status. Blood. 2004, 103: 2850-2858.PubMed Dreger P, Stilgenbauer S, Benner A, Ritgen M, Krober A, Kneba M, Schmitz N, Dohner H: The prognostic impact of autologous stem cell transplantation in patients with chronic lymphocytic leukemia: a risk-matched analysis based on the VH gene mutational status. Blood. 2004, 103: 2850-2858.PubMed
79.
go back to reference Muramatsu M, Kinoshita K, Fagarasan S, Yamada S, Shinkai Y, Honjo T: Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell. 2000, 102: 553-563.PubMed Muramatsu M, Kinoshita K, Fagarasan S, Yamada S, Shinkai Y, Honjo T: Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell. 2000, 102: 553-563.PubMed
80.
go back to reference Pasqualucci L, Guglielmino R, Houldsworth J, Mohr J, Aoufouchi S, Polakiewicz R, Chaganti RS, la-Favera R: Expression of the AID protein in normal and neoplastic B cells. Blood. 2004, 104: 3318-3325.PubMed Pasqualucci L, Guglielmino R, Houldsworth J, Mohr J, Aoufouchi S, Polakiewicz R, Chaganti RS, la-Favera R: Expression of the AID protein in normal and neoplastic B cells. Blood. 2004, 104: 3318-3325.PubMed
81.
go back to reference Albesiano E, Messmer BT, Damle RN, Allen SL, Rai KR, Chiorazzi N: Activation-induced cytidine deaminase in chronic lymphocytic leukemia B cells: expression as multiple forms in a dynamic, variably sized fraction of the clone. Blood. 2003, 102: 3333-3339.PubMed Albesiano E, Messmer BT, Damle RN, Allen SL, Rai KR, Chiorazzi N: Activation-induced cytidine deaminase in chronic lymphocytic leukemia B cells: expression as multiple forms in a dynamic, variably sized fraction of the clone. Blood. 2003, 102: 3333-3339.PubMed
82.
go back to reference Cerutti A, Zan H, Kim EC, Shah S, Schattner EJ, Schaffer A, Casali P: Ongoing in vivo immunoglobulin class switch DNA recombination in chronic lymphocytic leukemia B cells. J Immunol. 2002, 169: 6594-6603.PubMedCentralPubMed Cerutti A, Zan H, Kim EC, Shah S, Schattner EJ, Schaffer A, Casali P: Ongoing in vivo immunoglobulin class switch DNA recombination in chronic lymphocytic leukemia B cells. J Immunol. 2002, 169: 6594-6603.PubMedCentralPubMed
83.
go back to reference Oppezzo P, Vuillier F, Vasconcelos Y, Dumas G, Magnac C, Payelle-Brogard B, Pritsch O, Dighiero G: Chronic lymphocytic leukemia B cells expressing AID display dissociation between class switch recombination and somatic hypermutation. Blood. 2003, 101: 4029-4032.PubMed Oppezzo P, Vuillier F, Vasconcelos Y, Dumas G, Magnac C, Payelle-Brogard B, Pritsch O, Dighiero G: Chronic lymphocytic leukemia B cells expressing AID display dissociation between class switch recombination and somatic hypermutation. Blood. 2003, 101: 4029-4032.PubMed
84.
go back to reference Sahota SS, Davis Z, Hamblin TJ, Stevenson FK: Somatic mutation of bcl-6 genes can occur in the absence of V(H) mutations in chronic lymphocytic leukemia. Blood. 2000, 95: 3534-3540.PubMed Sahota SS, Davis Z, Hamblin TJ, Stevenson FK: Somatic mutation of bcl-6 genes can occur in the absence of V(H) mutations in chronic lymphocytic leukemia. Blood. 2000, 95: 3534-3540.PubMed
85.
go back to reference Reiniger L, Bodor C, Bognar A, Balogh Z, Csomor J, Szepesi A, Kopper L, Matolcsy A: Richter's and prolymphocytic transformation of chronic lymphocytic leukemia are associated with high mRNA expression of activation-induced cytidine deaminase and aberrant somatic hypermutation. Leukemia. 2006, 20: 1089-1095.PubMed Reiniger L, Bodor C, Bognar A, Balogh Z, Csomor J, Szepesi A, Kopper L, Matolcsy A: Richter's and prolymphocytic transformation of chronic lymphocytic leukemia are associated with high mRNA expression of activation-induced cytidine deaminase and aberrant somatic hypermutation. Leukemia. 2006, 20: 1089-1095.PubMed
86.
go back to reference Heintel D, Kroemer E, Kienle D, Schwarzinger I, Gleiss A, Schwarzmeier J, Marculescu R, Le T, Mannhalter C, Gaiger A, Stilgenbauer S, Dohner H, Fonatsch C, Jager U: High expression of activation-induced cytidine deaminase (AID) mRNA is associated with unmutated IGVH gene status and unfavourable cytogenetic aberrations in patients with chronic lymphocytic leukaemia. Leukemia. 2004, 18: 756-762.PubMed Heintel D, Kroemer E, Kienle D, Schwarzinger I, Gleiss A, Schwarzmeier J, Marculescu R, Le T, Mannhalter C, Gaiger A, Stilgenbauer S, Dohner H, Fonatsch C, Jager U: High expression of activation-induced cytidine deaminase (AID) mRNA is associated with unmutated IGVH gene status and unfavourable cytogenetic aberrations in patients with chronic lymphocytic leukaemia. Leukemia. 2004, 18: 756-762.PubMed
87.
go back to reference Messmer BT, Albesiano E, Messmer D, Chiorazzi N: The pattern and distribution of immunoglobulin VH gene mutations in chronic lymphocytic leukemia B cells are consistent with the canonical somatic hypermutation process. Blood. 2004, 103: 3490-3495.PubMed Messmer BT, Albesiano E, Messmer D, Chiorazzi N: The pattern and distribution of immunoglobulin VH gene mutations in chronic lymphocytic leukemia B cells are consistent with the canonical somatic hypermutation process. Blood. 2004, 103: 3490-3495.PubMed
88.
go back to reference Ghia P, Stamatopoulos K, Belessi C, Moreno C, Stella S, Guida G, Michel A, Crespo M, Laoutaris N, Montserrat E, Anagnostopoulos A, Dighiero G, Fassas A, Caligaris-Cappio F, Davi F: Geographic patterns and pathogenetic implications of IGHV gene usage in chronic lymphocytic leukemia: the lesson of the IGHV3-21 gene. Blood. 2005, 105: 1678-1685.PubMed Ghia P, Stamatopoulos K, Belessi C, Moreno C, Stella S, Guida G, Michel A, Crespo M, Laoutaris N, Montserrat E, Anagnostopoulos A, Dighiero G, Fassas A, Caligaris-Cappio F, Davi F: Geographic patterns and pathogenetic implications of IGHV gene usage in chronic lymphocytic leukemia: the lesson of the IGHV3-21 gene. Blood. 2005, 105: 1678-1685.PubMed
89.
go back to reference Stamatopoulos K, Belessi C, Moreno C, Boudjograh M, Guida G, Smilevska T, Belhoul L, Stella S, Stavroyianni N, Crespo M, Hadzidimitriou A, Sutton L, Bosch F, Laoutaris N, Anagnostopoulos A, Montserrat E, Fassas A, Dighiero G, Caligaris-Cappio F, Merle-Beral H, Ghia P, Davi F: Over 20% of patients with chronic lymphocytic leukemia carry stereotyped receptors: Pathogenetic implications and clinical correlations. Blood. 2007, 109: 259-270.PubMed Stamatopoulos K, Belessi C, Moreno C, Boudjograh M, Guida G, Smilevska T, Belhoul L, Stella S, Stavroyianni N, Crespo M, Hadzidimitriou A, Sutton L, Bosch F, Laoutaris N, Anagnostopoulos A, Montserrat E, Fassas A, Dighiero G, Caligaris-Cappio F, Merle-Beral H, Ghia P, Davi F: Over 20% of patients with chronic lymphocytic leukemia carry stereotyped receptors: Pathogenetic implications and clinical correlations. Blood. 2007, 109: 259-270.PubMed
90.
go back to reference Bomben R, Dal Bo M, Capello D, Benedetti D, Marconi D, Zucchetto A, Forconi F, Maffei R, Ghia EM, Laurenti L, Bulian P, Del Principe MI, Palermo G, Thorselius M, Degan M, Campanini R, Guarini A, Del Poeta G, Rosenquist R, Efremov DG, Marasca R, Foa R, Gaidano G, Gattei V: Comprehensive characterization of IGHV3-21-expressing B-cell chronic lymphocytic leukemia: an Italian multicenter study. Blood. 2007, 109: 2989-2998.PubMed Bomben R, Dal Bo M, Capello D, Benedetti D, Marconi D, Zucchetto A, Forconi F, Maffei R, Ghia EM, Laurenti L, Bulian P, Del Principe MI, Palermo G, Thorselius M, Degan M, Campanini R, Guarini A, Del Poeta G, Rosenquist R, Efremov DG, Marasca R, Foa R, Gaidano G, Gattei V: Comprehensive characterization of IGHV3-21-expressing B-cell chronic lymphocytic leukemia: an Italian multicenter study. Blood. 2007, 109: 2989-2998.PubMed
91.
go back to reference Murray F, Darzentas N, Hadzidimitriou A, Tobin G, Boudjogra M, Scielzo C, Laoutaris N, Karlsson K, Baran-Marzsak F, Tsaftaris A, Moreno C, Anagnostopoulos A, Caligaris-Cappio F, Vaur D, Ouzounis C, Belessi C, Ghia P, Davi F, Rosenquist R, Stamatopoulos K: Stereotyped patterns of somatic hypermutation in subsets of patients with chronic lymphocytic leukemia: implications for the role of antigen selection in leukemogenesis. Blood. 2008, 111: 1524-1533.PubMed Murray F, Darzentas N, Hadzidimitriou A, Tobin G, Boudjogra M, Scielzo C, Laoutaris N, Karlsson K, Baran-Marzsak F, Tsaftaris A, Moreno C, Anagnostopoulos A, Caligaris-Cappio F, Vaur D, Ouzounis C, Belessi C, Ghia P, Davi F, Rosenquist R, Stamatopoulos K: Stereotyped patterns of somatic hypermutation in subsets of patients with chronic lymphocytic leukemia: implications for the role of antigen selection in leukemogenesis. Blood. 2008, 111: 1524-1533.PubMed
92.
go back to reference Bomben R, Dal BM, Capello D, Forconi F, Maffei R, Laurenti L, Rossi D, Del Principe MI, Zucchetto A, Bertoni F, Rossi FM, Bulian P, Cattarossi I, Ilariucci F, Sozzi E, Spina V, Zucca E, Degan M, Lauria F, Del PG, Efremov DG, Marasca R, Gaidano G, Gattei V: Molecular and clinical features of chronic lymphocytic leukaemia with stereotyped B cell receptors: results from an Italian multicentre study. Br J Haematol. 2009, 144: 492-506.PubMed Bomben R, Dal BM, Capello D, Forconi F, Maffei R, Laurenti L, Rossi D, Del Principe MI, Zucchetto A, Bertoni F, Rossi FM, Bulian P, Cattarossi I, Ilariucci F, Sozzi E, Spina V, Zucca E, Degan M, Lauria F, Del PG, Efremov DG, Marasca R, Gaidano G, Gattei V: Molecular and clinical features of chronic lymphocytic leukaemia with stereotyped B cell receptors: results from an Italian multicentre study. Br J Haematol. 2009, 144: 492-506.PubMed
93.
go back to reference Tobin G, Thunberg U, Karlsson K, Murray F, Laurell A, Willander K, Enblad G, Merup M, Vilpo J, Juliusson G, Sundstrom C, Soderberg O, Roos G, Rosenquist R: Subsets with restricted immunoglobulin gene rearrangement features indicate a role for antigen selection in the development of chronic lymphocytic leukemia. Blood. 2004, 104: 2879-2885.PubMed Tobin G, Thunberg U, Karlsson K, Murray F, Laurell A, Willander K, Enblad G, Merup M, Vilpo J, Juliusson G, Sundstrom C, Soderberg O, Roos G, Rosenquist R: Subsets with restricted immunoglobulin gene rearrangement features indicate a role for antigen selection in the development of chronic lymphocytic leukemia. Blood. 2004, 104: 2879-2885.PubMed
94.
go back to reference Messmer BT, Albesiano E, Efremov DG, Ghiotto F, Allen SL, Kolitz J, Foa R, Damle RN, Fais F, Messmer D, Rai KR, Ferrarini M, Chiorazzi N: Multiple distinct sets of stereotyped antigen receptors indicate a role for antigen in promoting chronic lymphocytic leukemia. J Exp Med. 2004, 200: 519-525.PubMedCentralPubMed Messmer BT, Albesiano E, Efremov DG, Ghiotto F, Allen SL, Kolitz J, Foa R, Damle RN, Fais F, Messmer D, Rai KR, Ferrarini M, Chiorazzi N: Multiple distinct sets of stereotyped antigen receptors indicate a role for antigen in promoting chronic lymphocytic leukemia. J Exp Med. 2004, 200: 519-525.PubMedCentralPubMed
95.
go back to reference Widhopf GF, Rassenti LZ, Toy TL, Gribben JG, Wierda WG, Kipps TJ: Chronic lymphocytic leukemia B cells of more than 1% of patients express virtually identical immunoglobulins. Blood. 2004, 104: 2499-2504.PubMed Widhopf GF, Rassenti LZ, Toy TL, Gribben JG, Wierda WG, Kipps TJ: Chronic lymphocytic leukemia B cells of more than 1% of patients express virtually identical immunoglobulins. Blood. 2004, 104: 2499-2504.PubMed
96.
go back to reference Widhopf GF, Goldberg CJ, Toy TL, Rassenti LZ, Wierda WG, Byrd JC, Keating MJ, Gribben JG, Rai KR, Kipps TJ: Nonstochastic pairing of immunoglobulin heavy and light chains expressed by chronic lymphocytic leukemia B cells is predicated on the heavy chain CDR3. Blood. 2008, 111: 3137-3144.PubMedCentralPubMed Widhopf GF, Goldberg CJ, Toy TL, Rassenti LZ, Wierda WG, Byrd JC, Keating MJ, Gribben JG, Rai KR, Kipps TJ: Nonstochastic pairing of immunoglobulin heavy and light chains expressed by chronic lymphocytic leukemia B cells is predicated on the heavy chain CDR3. Blood. 2008, 111: 3137-3144.PubMedCentralPubMed
97.
go back to reference Messmer BT, Raphael BJ, Aerni SJ, Widhopf GF, Rassenti LZ, Gribben JG, Kay NE, Kipps TJ: Computational identification of CDR3 sequence archetypes among immunoglobulin sequences in chronic lymphocytic leukemia. Leuk Res. 2009, 33: 368-376.PubMedCentralPubMed Messmer BT, Raphael BJ, Aerni SJ, Widhopf GF, Rassenti LZ, Gribben JG, Kay NE, Kipps TJ: Computational identification of CDR3 sequence archetypes among immunoglobulin sequences in chronic lymphocytic leukemia. Leuk Res. 2009, 33: 368-376.PubMedCentralPubMed
98.
go back to reference Lanemo MA, Hellqvist E, Sidorova E, Soderberg A, Baxendale H, Dahle C, Willander K, Tobin G, Backman E, Soderberg O, Rosenquist R, Horkko S, Rosen A: A new perspective: molecular motifs on oxidized LDL, apoptotic cells, and bacteria are targets for chronic lymphocytic leukemia antibodies. Blood. 2008, 111: 3838-3848. Lanemo MA, Hellqvist E, Sidorova E, Soderberg A, Baxendale H, Dahle C, Willander K, Tobin G, Backman E, Soderberg O, Rosenquist R, Horkko S, Rosen A: A new perspective: molecular motifs on oxidized LDL, apoptotic cells, and bacteria are targets for chronic lymphocytic leukemia antibodies. Blood. 2008, 111: 3838-3848.
99.
go back to reference Herve M, Xu K, Ng YS, Wardemann H, Albesiano E, Messmer BT, Chiorazzi N, Meffre E: Unmutated and mutated chronic lymphocytic leukemias derive from self-reactive B cell precursors despite expressing different antibody reactivity. J Clin Invest. 2005, 115: 1636-1643.PubMedCentralPubMed Herve M, Xu K, Ng YS, Wardemann H, Albesiano E, Messmer BT, Chiorazzi N, Meffre E: Unmutated and mutated chronic lymphocytic leukemias derive from self-reactive B cell precursors despite expressing different antibody reactivity. J Clin Invest. 2005, 115: 1636-1643.PubMedCentralPubMed
100.
go back to reference Ghiotto F, Fais F, Valetto A, Albesiano E, Hashimoto S, Dono M, Ikematsu H, Allen SL, Kolitz J, Rai KR, Nardini M, Tramontano A, Ferrarini M, Chiorazzi N: Remarkably similar antigen receptors among a subset of patients with chronic lymphocytic leukemia. J Clin Invest. 2004, 113: 1008-1016.PubMedCentralPubMed Ghiotto F, Fais F, Valetto A, Albesiano E, Hashimoto S, Dono M, Ikematsu H, Allen SL, Kolitz J, Rai KR, Nardini M, Tramontano A, Ferrarini M, Chiorazzi N: Remarkably similar antigen receptors among a subset of patients with chronic lymphocytic leukemia. J Clin Invest. 2004, 113: 1008-1016.PubMedCentralPubMed
101.
go back to reference Athanasiadou A, Stamatopoulos K, Gaitatzi M, Stavroyianni N, Fassas A, Anagnostopoulos A: Recurrent cytogenetic findings in subsets of patients with chronic lymphocytic leukemia expressing IgG-switched stereotyped immunoglobulins. Haematologica. 2008, 93: 473-474.PubMed Athanasiadou A, Stamatopoulos K, Gaitatzi M, Stavroyianni N, Fassas A, Anagnostopoulos A: Recurrent cytogenetic findings in subsets of patients with chronic lymphocytic leukemia expressing IgG-switched stereotyped immunoglobulins. Haematologica. 2008, 93: 473-474.PubMed
102.
go back to reference Rossi D, Cerri M, Capello D, Deambrogi C, Rossi FM, Zucchetto A, De PL, Cresta S, Rasi S, Spina V, Franceschetti S, Lunghi M, Vendramin C, Bomben R, Ramponi A, Monga G, Conconi A, Magnani C, Gattei V, Gaidano G: Biological and clinical risk factors of chronic lymphocytic leukaemia transformation to Richter syndrome. Br J Haematol. 2008, Rossi D, Cerri M, Capello D, Deambrogi C, Rossi FM, Zucchetto A, De PL, Cresta S, Rasi S, Spina V, Franceschetti S, Lunghi M, Vendramin C, Bomben R, Ramponi A, Monga G, Conconi A, Magnani C, Gattei V, Gaidano G: Biological and clinical risk factors of chronic lymphocytic leukaemia transformation to Richter syndrome. Br J Haematol. 2008,
103.
go back to reference Rossi D, Spina V, Cerri M, Rasi S, Deambrogi C, De PL, Laurenti L, Maffei R, Forconi F, Bertoni F, Zucca E, Agostinelli C, Cabras A, Lucioni M, Martini M, Magni M, Deaglio S, Ladetto M, Nomdedeu JF, Besson C, Ramponi A, Canzonieri V, Paulli M, Marasca R, Larocca LM, Carbone A, Pileri SA, Gattei V, Gaidano G: Stereotyped B-Cell Receptor Is an Independent Risk Factor of Chronic Lymphocytic Leukemia Transformation to Richter Syndrome. Clin Cancer Res. 2009, 15 (13): 4415-22. Epub 2009 Jun 9PubMed Rossi D, Spina V, Cerri M, Rasi S, Deambrogi C, De PL, Laurenti L, Maffei R, Forconi F, Bertoni F, Zucca E, Agostinelli C, Cabras A, Lucioni M, Martini M, Magni M, Deaglio S, Ladetto M, Nomdedeu JF, Besson C, Ramponi A, Canzonieri V, Paulli M, Marasca R, Larocca LM, Carbone A, Pileri SA, Gattei V, Gaidano G: Stereotyped B-Cell Receptor Is an Independent Risk Factor of Chronic Lymphocytic Leukemia Transformation to Richter Syndrome. Clin Cancer Res. 2009, 15 (13): 4415-22. Epub 2009 Jun 9PubMed
104.
go back to reference Tobin G, Thunberg U, Johnson A, Eriksson I, Soderberg O, Karlsson K, Merup M, Juliusson G, Vilpo J, Enblad G, Sundstrom C, Roos G, Rosenquist R: Chronic lymphocytic leukemias utilizing the VH3-21 gene display highly restricted Vlambda2-14 gene use and homologous CDR3s: implicating recognition of a common antigen epitope. Blood. 2003, 101: 4952-4957.PubMed Tobin G, Thunberg U, Johnson A, Eriksson I, Soderberg O, Karlsson K, Merup M, Juliusson G, Vilpo J, Enblad G, Sundstrom C, Roos G, Rosenquist R: Chronic lymphocytic leukemias utilizing the VH3-21 gene display highly restricted Vlambda2-14 gene use and homologous CDR3s: implicating recognition of a common antigen epitope. Blood. 2003, 101: 4952-4957.PubMed
105.
go back to reference Thorselius M, Krober A, Murray F, Thunberg U, Tobin G, Buhler A, Kienle D, Albesiano E, Maffei R, Dao-Ung LP, Wiley J, Vilpo J, Laurell A, Merup M, Roos G, Karlsson K, Chiorazzi N, Marasca R, Dohner H, Stilgenbauer S, Rosenquist R: Strikingly homologous immunoglobulin gene rearrangements and poor outcome in VH3-21-using chronic lymphocytic leukemia patients independent of geographic origin and mutational status. Blood. 2006, 107: 2889-2894.PubMed Thorselius M, Krober A, Murray F, Thunberg U, Tobin G, Buhler A, Kienle D, Albesiano E, Maffei R, Dao-Ung LP, Wiley J, Vilpo J, Laurell A, Merup M, Roos G, Karlsson K, Chiorazzi N, Marasca R, Dohner H, Stilgenbauer S, Rosenquist R: Strikingly homologous immunoglobulin gene rearrangements and poor outcome in VH3-21-using chronic lymphocytic leukemia patients independent of geographic origin and mutational status. Blood. 2006, 107: 2889-2894.PubMed
106.
go back to reference Bomben R, Dal Bo M, Benedetti D, Capello D, Forconi F, Maffei R, Laurenti L, Marconi D, Rossi D, Bertoni F, Del Principe MI, Luciano F, Sozzi E, Zucchetto A, Rossi FM, Bulian P, Zucca E, Degan M, Efremov DG, Marasca R, Del Poeta G, Gaidano G, Gattei V: Expression of mutated IGHV3-23 genes has independent prognostic relevance in chronic lymphocytic leukemia and identifies a disease subset with peculiar molecular and biological features. Haematologica. 2009, 94 (s2): 141-(Abstract) Bomben R, Dal Bo M, Benedetti D, Capello D, Forconi F, Maffei R, Laurenti L, Marconi D, Rossi D, Bertoni F, Del Principe MI, Luciano F, Sozzi E, Zucchetto A, Rossi FM, Bulian P, Zucca E, Degan M, Efremov DG, Marasca R, Del Poeta G, Gaidano G, Gattei V: Expression of mutated IGHV3-23 genes has independent prognostic relevance in chronic lymphocytic leukemia and identifies a disease subset with peculiar molecular and biological features. Haematologica. 2009, 94 (s2): 141-(Abstract)
107.
go back to reference Hillson JL, Karr NS, Oppliger IR, Mannik M, Sasso EH: The structural basis of germline-encoded VH3 immunoglobulin binding to staphylococcal protein A. J Exp Med. 1993, 178: 331-336.PubMed Hillson JL, Karr NS, Oppliger IR, Mannik M, Sasso EH: The structural basis of germline-encoded VH3 immunoglobulin binding to staphylococcal protein A. J Exp Med. 1993, 178: 331-336.PubMed
108.
go back to reference Silverman GJ, Goodyear CS: A model B-cell superantigen and the immunobiology of B lymphocytes. Clin Immunol. 2002, 102: 117-134.PubMed Silverman GJ, Goodyear CS: A model B-cell superantigen and the immunobiology of B lymphocytes. Clin Immunol. 2002, 102: 117-134.PubMed
109.
go back to reference Silverman GJ, Goodyear CS: Confounding B-cell defences: lessons from a staphylococcal superantigen. Nat Rev Immunol. 2006, 6: 465-475.PubMed Silverman GJ, Goodyear CS: Confounding B-cell defences: lessons from a staphylococcal superantigen. Nat Rev Immunol. 2006, 6: 465-475.PubMed
110.
go back to reference Krober A, Benner A, Buhler A, Dohner H, Stilgenbauer S: Multivariate Survival Analysis of Specific VH-Genes in CLL: V3-21 and V3-23 Are Prognostic Factors Indipendently of the VH Mutation Status. Blood. 2002, 100: 196a-197a. (Abstract) Krober A, Benner A, Buhler A, Dohner H, Stilgenbauer S: Multivariate Survival Analysis of Specific VH-Genes in CLL: V3-21 and V3-23 Are Prognostic Factors Indipendently of the VH Mutation Status. Blood. 2002, 100: 196a-197a. (Abstract)
111.
go back to reference Chu DH, Morita CT, Weiss A: The Syk family of protein tyrosine kinases in T-cell activation and development. Immunol Rev. 1998, 165: 167-180.PubMed Chu DH, Morita CT, Weiss A: The Syk family of protein tyrosine kinases in T-cell activation and development. Immunol Rev. 1998, 165: 167-180.PubMed
112.
go back to reference Chan AC, van Oers NS, Tran A, Turka L, Law CL, Ryan JC, Clark EA, Weiss A: Differential expression of ZAP-70 and Syk protein tyrosine kinases, and the role of this family of protein tyrosine kinases in TCR signaling. J Immunol. 1994, 152: 4758-4766.PubMed Chan AC, van Oers NS, Tran A, Turka L, Law CL, Ryan JC, Clark EA, Weiss A: Differential expression of ZAP-70 and Syk protein tyrosine kinases, and the role of this family of protein tyrosine kinases in TCR signaling. J Immunol. 1994, 152: 4758-4766.PubMed
113.
go back to reference Wiestner A, Rosenwald A, Barry TS, Wright G, Davis RE, Henrickson SE, Zhao H, Ibbotson RE, Orchard JA, Davis Z, Stetler-Stevenson M, Raffeld M, Arthur DC, Marti GE, Wilson WH, Hamblin TJ, Oscier DG, Staudt LM: ZAP-70 expression identifies a chronic lymphocytic leukemia subtype with unmutated immunoglobulin genes, inferior clinical outcome, and distinct gene expression profile. Blood. 2003, 101: 4944-4951.PubMed Wiestner A, Rosenwald A, Barry TS, Wright G, Davis RE, Henrickson SE, Zhao H, Ibbotson RE, Orchard JA, Davis Z, Stetler-Stevenson M, Raffeld M, Arthur DC, Marti GE, Wilson WH, Hamblin TJ, Oscier DG, Staudt LM: ZAP-70 expression identifies a chronic lymphocytic leukemia subtype with unmutated immunoglobulin genes, inferior clinical outcome, and distinct gene expression profile. Blood. 2003, 101: 4944-4951.PubMed
114.
go back to reference Crespo M, Bosch F, Villamor N, Bellosillo B, Colomer D, Rozman M, Marce S, Lopez-Guillermo A, Campo E, Montserrat E: ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. N Engl J Med. 2003, 348: 1764-1775.PubMed Crespo M, Bosch F, Villamor N, Bellosillo B, Colomer D, Rozman M, Marce S, Lopez-Guillermo A, Campo E, Montserrat E: ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. N Engl J Med. 2003, 348: 1764-1775.PubMed
115.
go back to reference Zucchetto A, Bomben R, Dal Bo M, Nanni P, Bulian P, Rossi FM, Del Principe MI, Santini S, Del Poeta G, Degan M, Gattei V: ZAP-70 expression in B-cell chronic lymphocytic leukemia: evaluation by external (isotypic) or internal (T/NK cells) controls and correlation with IgV(H) mutations. Cytometry B Clin Cytom. 2006, 70: 284-292.PubMed Zucchetto A, Bomben R, Dal Bo M, Nanni P, Bulian P, Rossi FM, Del Principe MI, Santini S, Del Poeta G, Degan M, Gattei V: ZAP-70 expression in B-cell chronic lymphocytic leukemia: evaluation by external (isotypic) or internal (T/NK cells) controls and correlation with IgV(H) mutations. Cytometry B Clin Cytom. 2006, 70: 284-292.PubMed
116.
go back to reference Del Principe MI, Del Poeta G, Buccisano F, Maurillo L, Venditti A, Zucchetto A, Marini R, Niscola P, Consalvo MA, Mazzone C, Ottaviani L, Panetta P, Bruno A, Bomben R, Suppo G, Degan M, Gattei V, de Fabritiis P, Cantonetti M, Lo Coco F, Del Principe D, Amadori S: Clinical significance of ZAP-70 protein expression in B-cell chronic lymphocytic leukemia. Blood. 2006, 108: 853-861.PubMed Del Principe MI, Del Poeta G, Buccisano F, Maurillo L, Venditti A, Zucchetto A, Marini R, Niscola P, Consalvo MA, Mazzone C, Ottaviani L, Panetta P, Bruno A, Bomben R, Suppo G, Degan M, Gattei V, de Fabritiis P, Cantonetti M, Lo Coco F, Del Principe D, Amadori S: Clinical significance of ZAP-70 protein expression in B-cell chronic lymphocytic leukemia. Blood. 2006, 108: 853-861.PubMed
117.
go back to reference Marti G, Orfao A, Goolsby C: ZAP-70 in CLL: towards standardization of a biomarker for patient management: history of clinical cytometry special issue. Cytometry B Clin Cytom. 2006, 70: 197-200.PubMed Marti G, Orfao A, Goolsby C: ZAP-70 in CLL: towards standardization of a biomarker for patient management: history of clinical cytometry special issue. Cytometry B Clin Cytom. 2006, 70: 197-200.PubMed
118.
go back to reference Zenz T, Mertens D, Dohner H, Stilgenbauer S: Molecular diagnostics in chronic lymphocytic leukemia – pathogenetic and clinical implications. Leuk Lymphoma. 2008, 49: 864-873.PubMed Zenz T, Mertens D, Dohner H, Stilgenbauer S: Molecular diagnostics in chronic lymphocytic leukemia – pathogenetic and clinical implications. Leuk Lymphoma. 2008, 49: 864-873.PubMed
119.
go back to reference Chen L, Widhopf G, Huynh L, Rassenti L, Rai KR, Weiss A, Kipps TJ: Expression of ZAP-70 is associated with increased B-cell receptor signaling in chronic lymphocytic leukemia. Blood. 2002, 100: 4609-4614.PubMed Chen L, Widhopf G, Huynh L, Rassenti L, Rai KR, Weiss A, Kipps TJ: Expression of ZAP-70 is associated with increased B-cell receptor signaling in chronic lymphocytic leukemia. Blood. 2002, 100: 4609-4614.PubMed
120.
go back to reference Efremov DG, Gobessi S, Longo PG: Signaling pathways activated by antigen-receptor engagement in chronic lymphocytic leukemia B-cells. Autoimmun Rev. 2007, 7: 102-108.PubMed Efremov DG, Gobessi S, Longo PG: Signaling pathways activated by antigen-receptor engagement in chronic lymphocytic leukemia B-cells. Autoimmun Rev. 2007, 7: 102-108.PubMed
121.
go back to reference Chen L, Apgar J, Huynh L, Dicker F, Giago-McGahan T, Rassenti L, Weiss A, Kipps TJ: ZAP-70 directly enhances IgM signaling in chronic lymphocytic leukemia. Blood. 2005, 105: 2036-2041.PubMed Chen L, Apgar J, Huynh L, Dicker F, Giago-McGahan T, Rassenti L, Weiss A, Kipps TJ: ZAP-70 directly enhances IgM signaling in chronic lymphocytic leukemia. Blood. 2005, 105: 2036-2041.PubMed
122.
go back to reference Gobessi S, Laurenti L, Longo PG, Sica S, Leone G, Efremov DG: ZAP-70 enhances B-cell-receptor signaling despite absent or inefficient tyrosine kinase activation in chronic lymphocytic leukemia and lymphoma B cells. Blood. 2007, 109: 2032-2039.PubMed Gobessi S, Laurenti L, Longo PG, Sica S, Leone G, Efremov DG: ZAP-70 enhances B-cell-receptor signaling despite absent or inefficient tyrosine kinase activation in chronic lymphocytic leukemia and lymphoma B cells. Blood. 2007, 109: 2032-2039.PubMed
123.
go back to reference Ferrero E, Malavasi F: Human CD38, a leukocyte receptor and ectoenzyme, is a member of a novel eukaryotic gene family of nicotinamide adenine dinucleotide+-converting enzymes: extensive structural homology with the genes for murine bone marrow stromal cell antigen 1 and aplysian ADP-ribosyl cyclase. J Immunol. 1997, 159: 3858-3865.PubMed Ferrero E, Malavasi F: Human CD38, a leukocyte receptor and ectoenzyme, is a member of a novel eukaryotic gene family of nicotinamide adenine dinucleotide+-converting enzymes: extensive structural homology with the genes for murine bone marrow stromal cell antigen 1 and aplysian ADP-ribosyl cyclase. J Immunol. 1997, 159: 3858-3865.PubMed
124.
go back to reference Deaglio S, Aydin S, Vaisitti T, Bergui L, Malavasi F: CD38 at the junction between prognostic marker and therapeutic target. Trends Mol Med. 2008, 14: 210-218.PubMed Deaglio S, Aydin S, Vaisitti T, Bergui L, Malavasi F: CD38 at the junction between prognostic marker and therapeutic target. Trends Mol Med. 2008, 14: 210-218.PubMed
125.
go back to reference Howard M, Grimaldi JC, Bazan JF, Lund FE, Santos-Argumedo L, Parkhouse RM, Walseth TF, Lee HC: Formation and hydrolysis of cyclic ADP-ribose catalyzed by lymphocyte antigen CD38. Science. 1993, 262: 1056-1059.PubMed Howard M, Grimaldi JC, Bazan JF, Lund FE, Santos-Argumedo L, Parkhouse RM, Walseth TF, Lee HC: Formation and hydrolysis of cyclic ADP-ribose catalyzed by lymphocyte antigen CD38. Science. 1993, 262: 1056-1059.PubMed
126.
go back to reference Ibrahim S, Jilani I, O'Brien S, Rogers A, Manshouri T, Giles F, Faderl S, Thomas D, Kantarjian H, Keating M, Albitar M: Clinical relevance of the expression of the CD31 ligand for CD38 in patients with B-cell chronic lymphocytic leukemia. Cancer. 2003, 97: 1914-1919.PubMed Ibrahim S, Jilani I, O'Brien S, Rogers A, Manshouri T, Giles F, Faderl S, Thomas D, Kantarjian H, Keating M, Albitar M: Clinical relevance of the expression of the CD31 ligand for CD38 in patients with B-cell chronic lymphocytic leukemia. Cancer. 2003, 97: 1914-1919.PubMed
127.
go back to reference Hamblin TJ, Orchard JA, Gardiner A, Oscier DG, Davis Z, Stevenson FK: Immunoglobulin V genes and CD38 expression in CLL. Blood. 2000, 95: 2455-2457.PubMed Hamblin TJ, Orchard JA, Gardiner A, Oscier DG, Davis Z, Stevenson FK: Immunoglobulin V genes and CD38 expression in CLL. Blood. 2000, 95: 2455-2457.PubMed
128.
go back to reference Del Poeta G, Maurillo L, Venditti A, Buccisano F, Epiceno AM, Capelli G, Tamburini A, Suppo G, Battaglia A, Del Principe MI, Del Moro B, Masi M, Amadori S: Clinical significance of CD38 expression in chronic lymphocytic leukemia. Blood. 2001, 98: 2633-2639.PubMed Del Poeta G, Maurillo L, Venditti A, Buccisano F, Epiceno AM, Capelli G, Tamburini A, Suppo G, Battaglia A, Del Principe MI, Del Moro B, Masi M, Amadori S: Clinical significance of CD38 expression in chronic lymphocytic leukemia. Blood. 2001, 98: 2633-2639.PubMed
129.
go back to reference Jelinek DF, Tschumper RC, Geyer SM, Bone ND, Dewald GW, Hanson CA, Stenson MJ, Witzig TE, Tefferi A, Kay NE: Analysis of clonal B-cell CD38 and immunoglobulin variable region sequence status in relation to clinical outcome for B-chronic lymphocytic leukaemia. Br J Haematol. 2001, 115: 854-861.PubMed Jelinek DF, Tschumper RC, Geyer SM, Bone ND, Dewald GW, Hanson CA, Stenson MJ, Witzig TE, Tefferi A, Kay NE: Analysis of clonal B-cell CD38 and immunoglobulin variable region sequence status in relation to clinical outcome for B-chronic lymphocytic leukaemia. Br J Haematol. 2001, 115: 854-861.PubMed
130.
go back to reference Hamblin TJ, Orchard JA, Ibbotson RE, Davis Z, Thomas PW, Stevenson FK, Oscier DG: CD38 expression and immunoglobulin variable region mutations are independent prognostic variables in chronic lymphocytic leukemia, but CD38 expression may vary during the course of the disease. Blood. 2002, 99: 1023-1029.PubMed Hamblin TJ, Orchard JA, Ibbotson RE, Davis Z, Thomas PW, Stevenson FK, Oscier DG: CD38 expression and immunoglobulin variable region mutations are independent prognostic variables in chronic lymphocytic leukemia, but CD38 expression may vary during the course of the disease. Blood. 2002, 99: 1023-1029.PubMed
131.
go back to reference Matrai Z: CD38 as a prognostic marker in CLL. Hematology. 2005, 10: 39-46.PubMed Matrai Z: CD38 as a prognostic marker in CLL. Hematology. 2005, 10: 39-46.PubMed
132.
go back to reference Deaglio S, Vaisitti T, Bergui L, Bonello L, Horenstein AL, Tamagnone L, Boumsell L, Malavasi F: CD38 and CD100 lead a network of surface receptors relaying positive signals for B-CLL growth and survival. Blood. 2005, 105: 3042-3050.PubMed Deaglio S, Vaisitti T, Bergui L, Bonello L, Horenstein AL, Tamagnone L, Boumsell L, Malavasi F: CD38 and CD100 lead a network of surface receptors relaying positive signals for B-CLL growth and survival. Blood. 2005, 105: 3042-3050.PubMed
133.
go back to reference Deaglio S, Vaisitti T, Aydin S, Bergui L, D'Arena G, Bonello L, Omede' P, Scatolini M, Jaksic O, Chiorino G, Efremov D, Malavasi F: CD38 and ZAP-70 are functionally linked and mark CLL cells with high migratory potential. Blood. 2007, 110 (12): 4012-21.PubMed Deaglio S, Vaisitti T, Aydin S, Bergui L, D'Arena G, Bonello L, Omede' P, Scatolini M, Jaksic O, Chiorino G, Efremov D, Malavasi F: CD38 and ZAP-70 are functionally linked and mark CLL cells with high migratory potential. Blood. 2007, 110 (12): 4012-21.PubMed
134.
go back to reference Ghia P, Guida G, Stella S, Gottardi D, Geuna M, Strola G, Scielzo C, Caligaris-Cappio F: The pattern of CD38 expression defines a distinct subset of chronic lymphocytic leukemia (CLL) patients at risk of disease progression. Blood. 2003, 101: 1262-1269.PubMed Ghia P, Guida G, Stella S, Gottardi D, Geuna M, Strola G, Scielzo C, Caligaris-Cappio F: The pattern of CD38 expression defines a distinct subset of chronic lymphocytic leukemia (CLL) patients at risk of disease progression. Blood. 2003, 101: 1262-1269.PubMed
135.
go back to reference Jaksic O, Paro MM, Kardum SI, Kusec R, Pejsa V, Jaksic B: CD38 on B-cell chronic lymphocytic leukemia cells has higher expression in lymph nodes than in peripheral blood or bone marrow. Blood. 2004, 103: 1968-1969.PubMed Jaksic O, Paro MM, Kardum SI, Kusec R, Pejsa V, Jaksic B: CD38 on B-cell chronic lymphocytic leukemia cells has higher expression in lymph nodes than in peripheral blood or bone marrow. Blood. 2004, 103: 1968-1969.PubMed
136.
go back to reference Patten PE, Buggins AG, Richards J, Wotherspoon A, Salisbury J, Mufti GJ, Hamblin TJ, Devereux S: CD38 expression in chronic lymphocytic leukemia is regulated by the tumor microenvironment. Blood. 2008, 111: 5173-5181.PubMed Patten PE, Buggins AG, Richards J, Wotherspoon A, Salisbury J, Mufti GJ, Hamblin TJ, Devereux S: CD38 expression in chronic lymphocytic leukemia is regulated by the tumor microenvironment. Blood. 2008, 111: 5173-5181.PubMed
137.
go back to reference Burger JA, Tsukada N, Burger M, Zvaifler NJ, Dell'Aquila M, Kipps TJ: Blood-derived nurse-like cells protect chronic lymphocytic leukemia B cells from spontaneous apoptosis through stromal cell-derived factor-1. Blood. 2000, 96: 2655-2663.PubMed Burger JA, Tsukada N, Burger M, Zvaifler NJ, Dell'Aquila M, Kipps TJ: Blood-derived nurse-like cells protect chronic lymphocytic leukemia B cells from spontaneous apoptosis through stromal cell-derived factor-1. Blood. 2000, 96: 2655-2663.PubMed
138.
go back to reference Tsukada N, Burger JA, Zvaifler NJ, Kipps TJ: Distinctive features of "nurselike" cells that differentiate in the context of chronic lymphocytic leukemia. Blood. 2002, 99: 1030-1037.PubMed Tsukada N, Burger JA, Zvaifler NJ, Kipps TJ: Distinctive features of "nurselike" cells that differentiate in the context of chronic lymphocytic leukemia. Blood. 2002, 99: 1030-1037.PubMed
139.
go back to reference Caligaris-Cappio F: Role of the microenvironment in chronic lymphocytic leukaemia. Br J Haematol. 2003, 123: 380-388.PubMed Caligaris-Cappio F: Role of the microenvironment in chronic lymphocytic leukaemia. Br J Haematol. 2003, 123: 380-388.PubMed
140.
go back to reference Deaglio S, Vaisitti T, Billington R, Bergui L, Omede' P, Genazzani AA, Malavasi F: CD38/CD19: a lipid raft-dependent signaling complex in human B cells. Blood. 2007, 109: 5390-5398.PubMed Deaglio S, Vaisitti T, Billington R, Bergui L, Omede' P, Genazzani AA, Malavasi F: CD38/CD19: a lipid raft-dependent signaling complex in human B cells. Blood. 2007, 109: 5390-5398.PubMed
141.
go back to reference Richardson SJ, Matthews C, Catherwood MA, Alexander HD, Carey BS, Farrugia J, Gardiner A, Mould S, Oscier D, Copplestone JA, Prentice AG: ZAP-70 expression is associated with enhanced ability to respond to migratory and survival signals in B-cell chronic lymphocytic leukemia (B-CLL). Blood. 2006, 107: 3584-3592.PubMed Richardson SJ, Matthews C, Catherwood MA, Alexander HD, Carey BS, Farrugia J, Gardiner A, Mould S, Oscier D, Copplestone JA, Prentice AG: ZAP-70 expression is associated with enhanced ability to respond to migratory and survival signals in B-cell chronic lymphocytic leukemia (B-CLL). Blood. 2006, 107: 3584-3592.PubMed
142.
go back to reference Ottoson NC, Pribila JT, Chan AS, Shimizu Y: Cutting edge: T cell migration regulated by CXCR4 chemokine receptor signaling to ZAP-70 tyrosine kinase. J Immunol. 2001, 167: 1857-1861.PubMed Ottoson NC, Pribila JT, Chan AS, Shimizu Y: Cutting edge: T cell migration regulated by CXCR4 chemokine receptor signaling to ZAP-70 tyrosine kinase. J Immunol. 2001, 167: 1857-1861.PubMed
143.
go back to reference Ticchioni M, Charvet C, Noraz N, Lamy L, Steinberg M, Bernard A, Deckert M: Signaling through ZAP-70 is required for CXCL12-mediated T-cell transendothelial migration. Blood. 2002, 99: 3111-3118.PubMed Ticchioni M, Charvet C, Noraz N, Lamy L, Steinberg M, Bernard A, Deckert M: Signaling through ZAP-70 is required for CXCL12-mediated T-cell transendothelial migration. Blood. 2002, 99: 3111-3118.PubMed
144.
go back to reference Kumar A, Humphreys TD, Kremer KN, Bramati PS, Bradfield L, Edgar CE, Hedin KE: CXCR4 physically associates with the T cell receptor to signal in T cells. Immunity. 2006, 25: 213-224.PubMed Kumar A, Humphreys TD, Kremer KN, Bramati PS, Bradfield L, Edgar CE, Hedin KE: CXCR4 physically associates with the T cell receptor to signal in T cells. Immunity. 2006, 25: 213-224.PubMed
145.
go back to reference de la Fuente MT, Casanova B, Moyano JV, Garcia-Gila M, Sanz L, Garcia-Marco J, Silva A, Garcia-Pardo A: Engagement of alpha4beta1 integrin by fibronectin induces in vitro resistance of B chronic lymphocytic leukemia cells to fludarabine. J Leukoc Biol. 2002, 71: 495-502.PubMed de la Fuente MT, Casanova B, Moyano JV, Garcia-Gila M, Sanz L, Garcia-Marco J, Silva A, Garcia-Pardo A: Engagement of alpha4beta1 integrin by fibronectin induces in vitro resistance of B chronic lymphocytic leukemia cells to fludarabine. J Leukoc Biol. 2002, 71: 495-502.PubMed
146.
go back to reference Spessotto P, Cervi M, Mucignat MT, Mungiguerra G, Sartoretto I, Doliana R, Colombatti A: beta 1 Integrin-dependent Cell Adhesion to EMILIN-1 Is Mediated by the gC1q Domain. J Biol Chem. 2003, 278: 6160-6167.PubMed Spessotto P, Cervi M, Mucignat MT, Mungiguerra G, Sartoretto I, Doliana R, Colombatti A: beta 1 Integrin-dependent Cell Adhesion to EMILIN-1 Is Mediated by the gC1q Domain. J Biol Chem. 2003, 278: 6160-6167.PubMed
147.
go back to reference Eksioglu-Demiralp E, Alpdogan O, Aktan M, Firatli T, Ozturk A, Budak T, Bayik M, Akoglu T: Variable expression of CD49d antigen in B cell chronic lymphocytic leukemia is related to disease stages. Leukemia. 1996, 10: 1331-1339.PubMed Eksioglu-Demiralp E, Alpdogan O, Aktan M, Firatli T, Ozturk A, Budak T, Bayik M, Akoglu T: Variable expression of CD49d antigen in B cell chronic lymphocytic leukemia is related to disease stages. Leukemia. 1996, 10: 1331-1339.PubMed
148.
go back to reference Zucchetto A, Benedetti D, Tripodo C, Bomben R, Dal BM, Marconi D, Bossi F, Lorenzon D, Degan M, Rossi FM, Rossi D, Bulian P, Franco V, Del PG, Deaglio S, Gaidano G, Tedesco F, Malavasi F, Gattei V: CD38/CD31, the CCL3 and CCL4 chemokines, and CD49d/vascular cell adhesion molecule-1 are interchained by sequential events sustaining chronic lymphocytic leukemia cell survival. Cancer Res. 2009, 69: 4001-4009.PubMed Zucchetto A, Benedetti D, Tripodo C, Bomben R, Dal BM, Marconi D, Bossi F, Lorenzon D, Degan M, Rossi FM, Rossi D, Bulian P, Franco V, Del PG, Deaglio S, Gaidano G, Tedesco F, Malavasi F, Gattei V: CD38/CD31, the CCL3 and CCL4 chemokines, and CD49d/vascular cell adhesion molecule-1 are interchained by sequential events sustaining chronic lymphocytic leukemia cell survival. Cancer Res. 2009, 69: 4001-4009.PubMed
149.
go back to reference Koopman G, Keehnen RM, Lindhout E, Newman W, Shimizu Y, van Seventer GA, de GC, Pals ST: Adhesion through the LFA-1 (CD11a/CD18)-ICAM-1 (CD54) and the VLA-4 (CD49d)-VCAM-1 (CD106) pathways prevents apoptosis of germinal center B cells. J Immunol. 1994, 152: 3760-3767.PubMed Koopman G, Keehnen RM, Lindhout E, Newman W, Shimizu Y, van Seventer GA, de GC, Pals ST: Adhesion through the LFA-1 (CD11a/CD18)-ICAM-1 (CD54) and the VLA-4 (CD49d)-VCAM-1 (CD106) pathways prevents apoptosis of germinal center B cells. J Immunol. 1994, 152: 3760-3767.PubMed
150.
go back to reference Shanafelt TD, Geyer SM, Bone ND, Tschumper RC, Witzig TE, Nowakowski GS, Zent CS, Call TG, Laplant B, Dewald GW, Jelinek DF, Kay NE: CD49d expression is an independent predictor of overall survival in patients with chronic lymphocytic leukaemia: a prognostic parameter with therapeutic potential. Br J Haematol. 2008, 140: 537-546.PubMedCentralPubMed Shanafelt TD, Geyer SM, Bone ND, Tschumper RC, Witzig TE, Nowakowski GS, Zent CS, Call TG, Laplant B, Dewald GW, Jelinek DF, Kay NE: CD49d expression is an independent predictor of overall survival in patients with chronic lymphocytic leukaemia: a prognostic parameter with therapeutic potential. Br J Haematol. 2008, 140: 537-546.PubMedCentralPubMed
151.
go back to reference Bulian P, Gaidano G, Del PG, Gattei V: CD49d expression in chronic lymphocytic leukemia: a prognostic parameter and a therapeutic target. Future Oncol. 2008, 4: 355-358.PubMed Bulian P, Gaidano G, Del PG, Gattei V: CD49d expression in chronic lymphocytic leukemia: a prognostic parameter and a therapeutic target. Future Oncol. 2008, 4: 355-358.PubMed
152.
go back to reference Rossi D, Zucchetto A, Rossi FM, Capello D, Cerri M, Deambrogi C, Cresta S, Rasi S, De PL, Bodoni CL, Bulian P, Del PG, Ladetto M, Gattei V, Gaidano G: CD49d expression is an independent risk factor of progressive disease in early stage chronic lymphocytic leukemia. Haematologica. 2008, 93: 1575-1579.PubMed Rossi D, Zucchetto A, Rossi FM, Capello D, Cerri M, Deambrogi C, Cresta S, Rasi S, De PL, Bodoni CL, Bulian P, Del PG, Ladetto M, Gattei V, Gaidano G: CD49d expression is an independent risk factor of progressive disease in early stage chronic lymphocytic leukemia. Haematologica. 2008, 93: 1575-1579.PubMed
153.
go back to reference Leger OJ, Yednock TA, Tanner L, Horner HC, Hines DK, Keen S, Saldanha J, Jones ST, Fritz LC, Bendig MM: Humanization of a mouse antibody against human alpha-4 integrin: a potential therapeutic for the treatment of multiple sclerosis. Hum Antibodies. 1997, 8: 3-16.PubMed Leger OJ, Yednock TA, Tanner L, Horner HC, Hines DK, Keen S, Saldanha J, Jones ST, Fritz LC, Bendig MM: Humanization of a mouse antibody against human alpha-4 integrin: a potential therapeutic for the treatment of multiple sclerosis. Hum Antibodies. 1997, 8: 3-16.PubMed
154.
go back to reference Kleinfield RW, Weigert MG: Analysis of VH gene replacement events in a B cell lymphoma. J Immunol. 1989, 142: 4475-4482.PubMed Kleinfield RW, Weigert MG: Analysis of VH gene replacement events in a B cell lymphoma. J Immunol. 1989, 142: 4475-4482.PubMed
155.
go back to reference Zhang Z, Burrows PD, Cooper MD: The molecular basis and biological significance of VH replacement. Immunol Rev. 2004, 197: 231-242.PubMed Zhang Z, Burrows PD, Cooper MD: The molecular basis and biological significance of VH replacement. Immunol Rev. 2004, 197: 231-242.PubMed
156.
go back to reference Chiorazzi N, Hatzi K, Albesiano E: B-cell chronic lymphocytic leukemia, a clonal disease of B lymphocytes with receptors that vary in specificity for (auto)antigens. Ann N Y Acad Sci. 2005, 1062: 1-12.PubMed Chiorazzi N, Hatzi K, Albesiano E: B-cell chronic lymphocytic leukemia, a clonal disease of B lymphocytes with receptors that vary in specificity for (auto)antigens. Ann N Y Acad Sci. 2005, 1062: 1-12.PubMed
157.
go back to reference Chiorazzi N, Ferrarini M: B cell chronic lymphocytic leukemia: lessons learned from studies of the B cell antigen receptor. Annu Rev Immunol. 2003, 21: 841-894.PubMed Chiorazzi N, Ferrarini M: B cell chronic lymphocytic leukemia: lessons learned from studies of the B cell antigen receptor. Annu Rev Immunol. 2003, 21: 841-894.PubMed
158.
go back to reference Diamond B, Scharff MD: Somatic mutation of the T15 heavy chain gives rise to an antibody with autoantibody specificity. Proc Natl Acad Sci USA. 1984, 81: 5841-5844.PubMedCentralPubMed Diamond B, Scharff MD: Somatic mutation of the T15 heavy chain gives rise to an antibody with autoantibody specificity. Proc Natl Acad Sci USA. 1984, 81: 5841-5844.PubMedCentralPubMed
159.
go back to reference Diaw L, Siwarski D, Coleman A, Kim J, Jones GM, Dighiero G, Huppi K: Restricted immunoglobulin variable region (Ig V) gene expression accompanies secondary rearrangements of light chain Ig V genes in mouse plasmacytomas. J Exp Med. 1999, 190: 1405-1416.PubMedCentralPubMed Diaw L, Siwarski D, Coleman A, Kim J, Jones GM, Dighiero G, Huppi K: Restricted immunoglobulin variable region (Ig V) gene expression accompanies secondary rearrangements of light chain Ig V genes in mouse plasmacytomas. J Exp Med. 1999, 190: 1405-1416.PubMedCentralPubMed
160.
go back to reference Deaglio S, Capobianco A, Bergui L, Durig J, Morabito F, Duhrsen U, Malavasi F: CD38 is a signaling molecule in B-cell chronic lymphocytic leukemia cells. Blood. 2003, 102: 2146-2155.PubMed Deaglio S, Capobianco A, Bergui L, Durig J, Morabito F, Duhrsen U, Malavasi F: CD38 is a signaling molecule in B-cell chronic lymphocytic leukemia cells. Blood. 2003, 102: 2146-2155.PubMed
161.
go back to reference Foster AE, Brenner MK, Dotti G: Adoptive T-cell immunotherapy of chronic lymphocytic leukaemia. Best Pract Res Clin Haematol. 2008, 21: 375-389.PubMedCentralPubMed Foster AE, Brenner MK, Dotti G: Adoptive T-cell immunotherapy of chronic lymphocytic leukaemia. Best Pract Res Clin Haematol. 2008, 21: 375-389.PubMedCentralPubMed
162.
go back to reference Lanham S, Hamblin T, Oscier D, Ibbotson R, Stevenson F, Packham G: Differential signaling via surface IgM is associated with VH gene mutational status and CD38 expression in chronic lymphocytic leukemia. Blood. 2003, 101: 1087-1093.PubMed Lanham S, Hamblin T, Oscier D, Ibbotson R, Stevenson F, Packham G: Differential signaling via surface IgM is associated with VH gene mutational status and CD38 expression in chronic lymphocytic leukemia. Blood. 2003, 101: 1087-1093.PubMed
163.
go back to reference Scielzo C, Ghia P, Conti A, Bachi A, Guida G, Geuna M, Alessio M, Caligaris-Cappio F: HS1 protein is differentially expressed in chronic lymphocytic leukemia patient subsets with good or poor prognoses. J Clin Invest. 2005, 115: 1644-1650.PubMedCentralPubMed Scielzo C, Ghia P, Conti A, Bachi A, Guida G, Geuna M, Alessio M, Caligaris-Cappio F: HS1 protein is differentially expressed in chronic lymphocytic leukemia patient subsets with good or poor prognoses. J Clin Invest. 2005, 115: 1644-1650.PubMedCentralPubMed
164.
go back to reference Muzio M, Apollonio B, Scielzo C, Frenquelli M, Vandoni I, Boussiotis V, Caligaris-Cappio F, Ghia P: Constitutive activation of distinct BCR-signaling pathways in a subset of CLL patients: a molecular signature of anergy. Blood. 2008, 112: 188-195.PubMed Muzio M, Apollonio B, Scielzo C, Frenquelli M, Vandoni I, Boussiotis V, Caligaris-Cappio F, Ghia P: Constitutive activation of distinct BCR-signaling pathways in a subset of CLL patients: a molecular signature of anergy. Blood. 2008, 112: 188-195.PubMed
165.
go back to reference Ghia P, Scielzo C, Frenquelli M, Muzio M, Caligaris-Cappio F: From normal to clonal B cells: Chronic lymphocytic leukemia (CLL) at the crossroad between neoplasia and autoimmunity. Autoimmun Rev. 2007, 7: 127-131.PubMed Ghia P, Scielzo C, Frenquelli M, Muzio M, Caligaris-Cappio F: From normal to clonal B cells: Chronic lymphocytic leukemia (CLL) at the crossroad between neoplasia and autoimmunity. Autoimmun Rev. 2007, 7: 127-131.PubMed
166.
go back to reference Landgren O, Albitar M, Ma W, Abbasi F, Hayes RB, Ghia P, Marti GE, Caporaso NE: B-cell clones as early markers for chronic lymphocytic leukemia. N Engl J Med. 2009, 360: 659-667.PubMed Landgren O, Albitar M, Ma W, Abbasi F, Hayes RB, Ghia P, Marti GE, Caporaso NE: B-cell clones as early markers for chronic lymphocytic leukemia. N Engl J Med. 2009, 360: 659-667.PubMed
Metadata
Title
Intrinsic and extrinsic factors influencing the clinical course of B-cell chronic lymphocytic leukemia: prognostic markers with pathogenetic relevance
Authors
Michele Dal-Bo
Francesco Bertoni
Francesco Forconi
Antonella Zucchetto
Riccardo Bomben
Roberto Marasca
Silvia Deaglio
Luca Laurenti
Dimitar G Efremov
Gianluca Gaidano
Giovanni Del Poeta
Valter Gattei
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2009
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-7-76

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