Skip to main content
Top
Published in: International Journal of Hematology 6/2017

01-06-2017 | Progress in Hematology

CMML: Clinical and molecular aspects

Authors: Raphael Itzykson, Matthieu Duchmann, Nolwenn Lucas, Eric Solary

Published in: International Journal of Hematology | Issue 6/2017

Login to get access

Abstract

Chronic Myelomonocytic Leukemia is a chronic myeloid neoplasm occurring mostly in the elderly with overlapping features of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) characterized by chronic monocytosis. Recent progresses in the molecular and cellular pathogenesis of CMML have stirred a renewed interest in this clinically heterogeneous disorder. Here, we review the recent progresses in the biology of CMML and how it affects its current and future clinical management.
Literature
1.
go back to reference Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–405.CrossRefPubMed Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–405.CrossRefPubMed
2.
go back to reference Wattel E, Guerci A, Hecquet B, Economopoulos T, Copplestone A, Mahe B, et al. A randomized trial of hydroxyurea versus VP16 in adult chronic myelomonocytic leukemia. Groupe Francais des Myelodysplasies and European CMML Group. Blood. 1996;88(7):2480–7.PubMed Wattel E, Guerci A, Hecquet B, Economopoulos T, Copplestone A, Mahe B, et al. A randomized trial of hydroxyurea versus VP16 in adult chronic myelomonocytic leukemia. Groupe Francais des Myelodysplasies and European CMML Group. Blood. 1996;88(7):2480–7.PubMed
3.
go back to reference Itzykson R, Kosmider O, Renneville A, Gelsi-Boyer V, Meggendorfer M, Morabito M, et al. Prognostic score including gene mutations in chronic myelomonocytic leukemia. J Clin Oncol [Research Support, Non-U.S. Gov’t]. 2013;31(19):2428–36. Itzykson R, Kosmider O, Renneville A, Gelsi-Boyer V, Meggendorfer M, Morabito M, et al. Prognostic score including gene mutations in chronic myelomonocytic leukemia. J Clin Oncol [Research Support, Non-U.S. Gov’t]. 2013;31(19):2428–36.
4.
go back to reference Savona MR, Malcovati L, Komrokji R, Tiu RV, Mughal TI, Orazi A, et al. An international consortium proposal of uniform response criteria for myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in adults. Blood. 2015 Jan 26. Savona MR, Malcovati L, Komrokji R, Tiu RV, Mughal TI, Orazi A, et al. An international consortium proposal of uniform response criteria for myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in adults. Blood. 2015 Jan 26.
5.
go back to reference Srour SA, Devesa SS, Morton LM, Check DP, Curtis RE, Linet MS, et al. Incidence and patient survival of myeloproliferative neoplasms and myelodysplastic/myeloproliferative neoplasms in the United States, 2001–12. Br J Haematol. 2016;174(3):382–96.CrossRefPubMed Srour SA, Devesa SS, Morton LM, Check DP, Curtis RE, Linet MS, et al. Incidence and patient survival of myeloproliferative neoplasms and myelodysplastic/myeloproliferative neoplasms in the United States, 2001–12. Br J Haematol. 2016;174(3):382–96.CrossRefPubMed
6.
go back to reference Phekoo KJ, Richards MA, Moller H, Schey SA. The incidence and outcome of myeloid malignancies in 2,112 adult patients in southeast England. Haematologica. 2006;91(10):1400–4.PubMed Phekoo KJ, Richards MA, Moller H, Schey SA. The incidence and outcome of myeloid malignancies in 2,112 adult patients in southeast England. Haematologica. 2006;91(10):1400–4.PubMed
7.
go back to reference Dinmohamed AG, van Norden Y, Visser O, Posthuma EF, Huijgens PC, Sonneveld P, et al. The use of medical claims to assess incidence, diagnostic procedures and initial treatment of myelodysplastic syndromes and chronic myelomonocytic leukemia in the Netherlands. Leuk Res. 2015;39(2):177–82.CrossRefPubMed Dinmohamed AG, van Norden Y, Visser O, Posthuma EF, Huijgens PC, Sonneveld P, et al. The use of medical claims to assess incidence, diagnostic procedures and initial treatment of myelodysplastic syndromes and chronic myelomonocytic leukemia in the Netherlands. Leuk Res. 2015;39(2):177–82.CrossRefPubMed
8.
go back to reference Patnaik MM, Wassie EA, Padron E, Onida F, Itzykson R, Lasho TL, et al. Chronic myelomonocytic leukemia in younger patients: molecular and cytogenetic predictors of survival and treatment outcome. Blood Cancer J. 2015;13(5):e280.CrossRef Patnaik MM, Wassie EA, Padron E, Onida F, Itzykson R, Lasho TL, et al. Chronic myelomonocytic leukemia in younger patients: molecular and cytogenetic predictors of survival and treatment outcome. Blood Cancer J. 2015;13(5):e280.CrossRef
9.
go back to reference Merlevede J, Droin N, Qin T, Meldi K, Yoshida K, Morabito M, et al. Mutation allele burden remains unchanged in chronic myelomonocytic leukaemia responding to hypomethylating agents. Nat Commun. 2016;7:10767.CrossRefPubMedPubMedCentral Merlevede J, Droin N, Qin T, Meldi K, Yoshida K, Morabito M, et al. Mutation allele burden remains unchanged in chronic myelomonocytic leukaemia responding to hypomethylating agents. Nat Commun. 2016;7:10767.CrossRefPubMedPubMedCentral
10.
go back to reference Mason CC, Khorashad JS, Tantravahi SK, Kelley TW, Zabriskie MS, Yan D, et al. Age-related mutations and chronic myelomonocytic leukemia. Leukemia. 2016;30(4):906–13.CrossRefPubMed Mason CC, Khorashad JS, Tantravahi SK, Kelley TW, Zabriskie MS, Yan D, et al. Age-related mutations and chronic myelomonocytic leukemia. Leukemia. 2016;30(4):906–13.CrossRefPubMed
11.
go back to reference Padron E, Yoder S, Kunigal S, Mesa T, Teer JK, Al Ali N, et al. ETV6 and signaling gene mutations are associated with secondary transformation of myelodysplastic syndromes to chronic myelomonocytic leukemia. Blood. 2014;123(23):3675–7.CrossRefPubMedPubMedCentral Padron E, Yoder S, Kunigal S, Mesa T, Teer JK, Al Ali N, et al. ETV6 and signaling gene mutations are associated with secondary transformation of myelodysplastic syndromes to chronic myelomonocytic leukemia. Blood. 2014;123(23):3675–7.CrossRefPubMedPubMedCentral
12.
go back to reference Takahashi K, Pemmaraju N, Strati P, Nogueras-Gonzalez G, Ning J, Bueso-Ramos C, et al. Clinical characteristics and outcomes of therapy-related chronic myelomonocytic leukemia. Blood. 2013;122(16):2807–11 (quiz 920).CrossRefPubMedPubMedCentral Takahashi K, Pemmaraju N, Strati P, Nogueras-Gonzalez G, Ning J, Bueso-Ramos C, et al. Clinical characteristics and outcomes of therapy-related chronic myelomonocytic leukemia. Blood. 2013;122(16):2807–11 (quiz 920).CrossRefPubMedPubMedCentral
13.
go back to reference Droin N, Jacquel A, Hendra JB, Racoeur C, Truntzer C, Pecqueur D, et al. Alpha-defensins secreted by dysplastic granulocytes inhibit the differentiation of monocytes in chronic myelomonocytic leukemia. Blood. 2010;115(1):78–88.CrossRefPubMed Droin N, Jacquel A, Hendra JB, Racoeur C, Truntzer C, Pecqueur D, et al. Alpha-defensins secreted by dysplastic granulocytes inhibit the differentiation of monocytes in chronic myelomonocytic leukemia. Blood. 2010;115(1):78–88.CrossRefPubMed
14.
go back to reference Droin N, Itzykson R, Rameau P, Morabito M, Braun T, Louache F, et al. Myeloid-derived suppressive cells belonging to the leukemic clone account for immunosuppression In CMML. Blood (ASH Annual Meeting). 2010:p3997. Droin N, Itzykson R, Rameau P, Morabito M, Braun T, Louache F, et al. Myeloid-derived suppressive cells belonging to the leukemic clone account for immunosuppression In CMML. Blood (ASH Annual Meeting). 2010:p3997.
15.
go back to reference Damm F, Itzykson R, Kosmider O, Droin N, Renneville A, Chesnais V, et al. SETBP1 mutations in 658 patients with myelodysplastic syndromes, chronic myelomonocytic leukemia and secondary acute myeloid leukemias. Leukemia. 2013;27(6):1401–3.CrossRefPubMed Damm F, Itzykson R, Kosmider O, Droin N, Renneville A, Chesnais V, et al. SETBP1 mutations in 658 patients with myelodysplastic syndromes, chronic myelomonocytic leukemia and secondary acute myeloid leukemias. Leukemia. 2013;27(6):1401–3.CrossRefPubMed
16.
go back to reference Kosmider O, Itzykson R, Chesnais V, Lasho T, Laborde R, Knudson R, et al. Mutation of the colony-stimulating factor-3 receptor gene is a rare event with poor prognosis in chronic myelomonocytic leukemia. Leukemia. 2013 Jun 18. Kosmider O, Itzykson R, Chesnais V, Lasho T, Laborde R, Knudson R, et al. Mutation of the colony-stimulating factor-3 receptor gene is a rare event with poor prognosis in chronic myelomonocytic leukemia. Leukemia. 2013 Jun 18.
17.
go back to reference Ball M, List AF, Padron E. When clinical heterogeneity exceeds genetic heterogeneity: thinking outside the genomic box in chronic myelomonocytic leukemia. Blood. 2016;128(20):2381–7.CrossRefPubMed Ball M, List AF, Padron E. When clinical heterogeneity exceeds genetic heterogeneity: thinking outside the genomic box in chronic myelomonocytic leukemia. Blood. 2016;128(20):2381–7.CrossRefPubMed
18.
go back to reference Goasguen JE, Bennett JM, Bain BJ, Vallespi T, Brunning R, Mufti GJ. Morphological evaluation of monocytes and their precursors. Haematologica. 2009;94(7):994–7.CrossRefPubMedPubMedCentral Goasguen JE, Bennett JM, Bain BJ, Vallespi T, Brunning R, Mufti GJ. Morphological evaluation of monocytes and their precursors. Haematologica. 2009;94(7):994–7.CrossRefPubMedPubMedCentral
19.
go back to reference Elliott MA, Verstovsek S, Dingli D, Schwager SM, Mesa RA, Li CY, et al. Monocytosis is an adverse prognostic factor for survival in younger patients with primary myelofibrosis. Leuk Res. 2007;31(11):1503–9.CrossRefPubMed Elliott MA, Verstovsek S, Dingli D, Schwager SM, Mesa RA, Li CY, et al. Monocytosis is an adverse prognostic factor for survival in younger patients with primary myelofibrosis. Leuk Res. 2007;31(11):1503–9.CrossRefPubMed
20.
go back to reference Wang SA, Hutchinson L, Tang G, Chen SS, Miron PM, Huh YO, et al. Systemic mastocytosis with associated clonal hematological non-mast cell lineage disease: clinical significance and comparison of chomosomal abnormalities in SM and AHNMD components. Am J Hematol. 2013;88(3):219–24.CrossRefPubMedPubMedCentral Wang SA, Hutchinson L, Tang G, Chen SS, Miron PM, Huh YO, et al. Systemic mastocytosis with associated clonal hematological non-mast cell lineage disease: clinical significance and comparison of chomosomal abnormalities in SM and AHNMD components. Am J Hematol. 2013;88(3):219–24.CrossRefPubMedPubMedCentral
21.
go back to reference Edelbroek JR, Vermeer MH, Jansen PM, Stoof TJ, van der Linden MM, Horvath B, et al. Langerhans cell histiocytosis first presenting in the skin in adults: frequent association with a second haematological malignancy. Br J Dermatol. 2012;167(6):1287–94.CrossRefPubMed Edelbroek JR, Vermeer MH, Jansen PM, Stoof TJ, van der Linden MM, Horvath B, et al. Langerhans cell histiocytosis first presenting in the skin in adults: frequent association with a second haematological malignancy. Br J Dermatol. 2012;167(6):1287–94.CrossRefPubMed
22.
go back to reference Brunetti L, Di Battista V, Venanzi A, Schiavoni G, Martelli MP, Ascani S, et al. Blastic plasmacytoid dendritic cell neoplasm and chronic myelomonocytic leukemia: a shared clonal origin. Leukemia. 2017 Feb 10. Brunetti L, Di Battista V, Venanzi A, Schiavoni G, Martelli MP, Ascani S, et al. Blastic plasmacytoid dendritic cell neoplasm and chronic myelomonocytic leukemia: a shared clonal origin. Leukemia. 2017 Feb 10.
23.
go back to reference Such E, Cervera J, Costa D, Sole F, Vallespi T, Luno E, et al. Cytogenetic risk stratification in chronic myelomonocytic leukemia. Haematologica. 2011;96(3):375–83.CrossRefPubMed Such E, Cervera J, Costa D, Sole F, Vallespi T, Luno E, et al. Cytogenetic risk stratification in chronic myelomonocytic leukemia. Haematologica. 2011;96(3):375–83.CrossRefPubMed
24.
go back to reference Meggendorfer M, Roller A, Haferlach T, Eder C, Dicker F, Grossmann V, et al. SRSF2 mutations in 275 cases with chronic myelomonocytic leukemia (CMML). Blood. 2012;120(15):3080–8.CrossRefPubMedPubMedCentral Meggendorfer M, Roller A, Haferlach T, Eder C, Dicker F, Grossmann V, et al. SRSF2 mutations in 275 cases with chronic myelomonocytic leukemia (CMML). Blood. 2012;120(15):3080–8.CrossRefPubMedPubMedCentral
25.
go back to reference Selimoglu-Buet D, Wagner-Ballon O, Saada V, Bardet V, Itzykson R, Bencheikh L, et al. Characteristic repartition of monocyte subsets as a diagnostic signature of chronic myelomonocytic leukemia. Blood. 2015;125(23):3618–26.CrossRefPubMedPubMedCentral Selimoglu-Buet D, Wagner-Ballon O, Saada V, Bardet V, Itzykson R, Bencheikh L, et al. Characteristic repartition of monocyte subsets as a diagnostic signature of chronic myelomonocytic leukemia. Blood. 2015;125(23):3618–26.CrossRefPubMedPubMedCentral
26.
go back to reference Vitte F, Fabiani B, Benet C, Dalac S, Balme B, Delattre C, et al. Specific skin lesions in chronic myelomonocytic leukemia: a spectrum of myelomonocytic and dendritic cell proliferations: a study of 42 cases. Am J Surg Pathol. 2012;36(9):1302–16.CrossRefPubMed Vitte F, Fabiani B, Benet C, Dalac S, Balme B, Delattre C, et al. Specific skin lesions in chronic myelomonocytic leukemia: a spectrum of myelomonocytic and dendritic cell proliferations: a study of 42 cases. Am J Surg Pathol. 2012;36(9):1302–16.CrossRefPubMed
27.
go back to reference Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009;10(3):223–32.CrossRefPubMedPubMedCentral Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009;10(3):223–32.CrossRefPubMedPubMedCentral
28.
go back to reference Niyongere S, Lucas N, Sansil S, Cubitt CL, Balasis ME, Kroeger J, et al. Comprehensive inflammatory cytokine profiling identifies IL-8/CXCL8 as elevated, associated with proliferative features, and independently prognostic in chronic myelomonocytic Leukemia (CMML). Blood. 2016;128(22):109. Niyongere S, Lucas N, Sansil S, Cubitt CL, Balasis ME, Kroeger J, et al. Comprehensive inflammatory cytokine profiling identifies IL-8/CXCL8 as elevated, associated with proliferative features, and independently prognostic in chronic myelomonocytic Leukemia (CMML). Blood. 2016;128(22):109.
29.
go back to reference Padron E, Dezern A, Andrade-Campos M, Vaddi K, Scherle P, Zhang Q, et al. A Multi-Institution Phase 1 Trial of Ruxolitinib in Patients with Chronic Myelomonocytic Leukemia (CMML). Clin Cancer Res. 2016 Feb 8. Padron E, Dezern A, Andrade-Campos M, Vaddi K, Scherle P, Zhang Q, et al. A Multi-Institution Phase 1 Trial of Ruxolitinib in Patients with Chronic Myelomonocytic Leukemia (CMML). Clin Cancer Res. 2016 Feb 8.
30.
go back to reference Grignano E, Mekinian A, Braun T, Liozon E, Hamidou M, Decaux O, et al. Autoimmune and inflammatory diseases associated with chronic myelomonocytic leukemia: a series of 26 cases and literature review. Leuk Res. 2016;47:136–41.CrossRefPubMed Grignano E, Mekinian A, Braun T, Liozon E, Hamidou M, Decaux O, et al. Autoimmune and inflammatory diseases associated with chronic myelomonocytic leukemia: a series of 26 cases and literature review. Leuk Res. 2016;47:136–41.CrossRefPubMed
31.
go back to reference Zahid MF, Barraco D, Lasho TL, Finke C, Ketterling RP, Gangat N, et al. Spectrum of autoimmune diseases and systemic inflammatory syndromes in patients with chronic myelomonocytic leukemia. Leuk Lymphoma. 2017;58(6):1488–93.CrossRefPubMed Zahid MF, Barraco D, Lasho TL, Finke C, Ketterling RP, Gangat N, et al. Spectrum of autoimmune diseases and systemic inflammatory syndromes in patients with chronic myelomonocytic leukemia. Leuk Lymphoma. 2017;58(6):1488–93.CrossRefPubMed
32.
go back to reference Fraison JB, Mekinian A, Grignano E, Kahn JE, Arlet JB, Decaux O, et al. Efficacy of Azacitidine in autoimmune and inflammatory disorders associated with myelodysplastic syndromes and chronic myelomonocytic leukemia. Leuk Res. 2016;43:13–7.CrossRefPubMed Fraison JB, Mekinian A, Grignano E, Kahn JE, Arlet JB, Decaux O, et al. Efficacy of Azacitidine in autoimmune and inflammatory disorders associated with myelodysplastic syndromes and chronic myelomonocytic leukemia. Leuk Res. 2016;43:13–7.CrossRefPubMed
33.
go back to reference Elbaek MV, Sorensen AL, Hasselbalch HC. Chronic inflammation and autoimmunity as risk factors for the development of chronic myelomonocytic leukemia? Leuk Lymphoma. 2016;57(8):1793–9.CrossRefPubMed Elbaek MV, Sorensen AL, Hasselbalch HC. Chronic inflammation and autoimmunity as risk factors for the development of chronic myelomonocytic leukemia? Leuk Lymphoma. 2016;57(8):1793–9.CrossRefPubMed
34.
go back to reference Hasselbalch HC. Perspectives on chronic inflammation in essential thrombocythemia, polycythemia vera, and myelofibrosis: is chronic inflammation a trigger and driver of clonal evolution and development of accelerated atherosclerosis and second cancer? Blood. 2012;119(14):3219–25.CrossRefPubMed Hasselbalch HC. Perspectives on chronic inflammation in essential thrombocythemia, polycythemia vera, and myelofibrosis: is chronic inflammation a trigger and driver of clonal evolution and development of accelerated atherosclerosis and second cancer? Blood. 2012;119(14):3219–25.CrossRefPubMed
35.
go back to reference Itzykson R, Kosmider O, Renneville A, Morabito M, Preudhomme C, Berthon C, et al. Clonal architecture of chronic myelomonocytic leukemias. Blood. [Research Support, Non-U.S. Gov’t]. 2013;121(12):2186–98. Itzykson R, Kosmider O, Renneville A, Morabito M, Preudhomme C, Berthon C, et al. Clonal architecture of chronic myelomonocytic leukemias. Blood. [Research Support, Non-U.S. Gov’t]. 2013;121(12):2186–98.
36.
go back to reference Yue X, Trifari S, Aijo T, Tsagaratou A, Pastor WA, Zepeda-Martinez JA, et al. Control of Foxp3 stability through modulation of TET activity. J Exp Med. 2016;213(3):377–97.CrossRefPubMedPubMedCentral Yue X, Trifari S, Aijo T, Tsagaratou A, Pastor WA, Zepeda-Martinez JA, et al. Control of Foxp3 stability through modulation of TET activity. J Exp Med. 2016;213(3):377–97.CrossRefPubMedPubMedCentral
37.
go back to reference Tsagaratou A, Gonzalez-Avalos E, Rautio S, Scott-Browne JP, Togher S, Pastor WA, et al. TET proteins regulate the lineage specification and TCR-mediated expansion of iNKT cells. Nat Immunol. 2017;18(1):45–53.CrossRefPubMed Tsagaratou A, Gonzalez-Avalos E, Rautio S, Scott-Browne JP, Togher S, Pastor WA, et al. TET proteins regulate the lineage specification and TCR-mediated expansion of iNKT cells. Nat Immunol. 2017;18(1):45–53.CrossRefPubMed
38.
go back to reference Palomo L, Xicoy B, Garcia O, Mallo M, Adema V, Cabezon M, et al. Impact of SNP array karyotyping on the diagnosis and the outcome of chronic myelomonocytic leukemia with low risk cytogenetic features or no metaphases. Am J Hematol. 2016;91(2):185–92.CrossRefPubMed Palomo L, Xicoy B, Garcia O, Mallo M, Adema V, Cabezon M, et al. Impact of SNP array karyotyping on the diagnosis and the outcome of chronic myelomonocytic leukemia with low risk cytogenetic features or no metaphases. Am J Hematol. 2016;91(2):185–92.CrossRefPubMed
39.
go back to reference Malcovati L, Papaemmanuil E, Ambaglio I, Elena C, Galli A, Della Porta MG, et al. Driver somatic mutations identify distinct disease entities within myeloid neoplasms with myelodysplasia. Blood. 2014;124(9):1513–21.CrossRefPubMedPubMedCentral Malcovati L, Papaemmanuil E, Ambaglio I, Elena C, Galli A, Della Porta MG, et al. Driver somatic mutations identify distinct disease entities within myeloid neoplasms with myelodysplasia. Blood. 2014;124(9):1513–21.CrossRefPubMedPubMedCentral
40.
go back to reference Itzykson R, Solary E. An evolutionary perspective on chronic myelomonocytic leukemia. Leukemia. 2013;27(7):1441–50.CrossRefPubMed Itzykson R, Solary E. An evolutionary perspective on chronic myelomonocytic leukemia. Leukemia. 2013;27(7):1441–50.CrossRefPubMed
41.
go back to reference Birrer A, Jusufi F, Bernimoulin M, Tichelli A, Gratwohl A, Nissen-Druey C, et al. Hematopoietic progenitor cell colony growth differentiates chronic myelomonocytic leukemia from reactive monocytosis. Eur J Haematol. 2008;81(4):267–72.CrossRefPubMed Birrer A, Jusufi F, Bernimoulin M, Tichelli A, Gratwohl A, Nissen-Druey C, et al. Hematopoietic progenitor cell colony growth differentiates chronic myelomonocytic leukemia from reactive monocytosis. Eur J Haematol. 2008;81(4):267–72.CrossRefPubMed
42.
go back to reference Kotecha N, Flores NJ, Irish JM, Simonds EF, Sakai DS, Archambeault S, et al. Single-cell profiling identifies aberrant STAT5 activation in myeloid malignancies with specific clinical and biologic correlates. Cancer Cell. 2008;14(4):335–43.CrossRefPubMedPubMedCentral Kotecha N, Flores NJ, Irish JM, Simonds EF, Sakai DS, Archambeault S, et al. Single-cell profiling identifies aberrant STAT5 activation in myeloid malignancies with specific clinical and biologic correlates. Cancer Cell. 2008;14(4):335–43.CrossRefPubMedPubMedCentral
43.
go back to reference Padron E, Painter JS, Kunigal S, Mailloux AW, McGraw K, McDaniel JM, et al. GM-CSF-dependent pSTAT5 sensitivity is a feature with therapeutic potential in chronic myelomonocytic leukemia. Blood. 2013;121(25):5068–77.CrossRefPubMedPubMedCentral Padron E, Painter JS, Kunigal S, Mailloux AW, McGraw K, McDaniel JM, et al. GM-CSF-dependent pSTAT5 sensitivity is a feature with therapeutic potential in chronic myelomonocytic leukemia. Blood. 2013;121(25):5068–77.CrossRefPubMedPubMedCentral
44.
go back to reference Geissler K, Jager E, Barna A, Alendar T, Ljubuncic E, Sliwa T, et al. Chronic myelomonocytic leukemia patients with RAS pathway mutations show high in vitro myeloid colony formation in the absence of exogenous growth factors. Leukemia. 2016;30(11):2280–1.CrossRefPubMedPubMedCentral Geissler K, Jager E, Barna A, Alendar T, Ljubuncic E, Sliwa T, et al. Chronic myelomonocytic leukemia patients with RAS pathway mutations show high in vitro myeloid colony formation in the absence of exogenous growth factors. Leukemia. 2016;30(11):2280–1.CrossRefPubMedPubMedCentral
45.
go back to reference Itzykson R, Kosmider O, Renneville A, Morabito M, Buet D, Preudhomme C, et al. Two distinct mechanisms contribute to granulomonocytic hyperplasia in chronic myelomonocytic Leukemias (CMML). ASH Annual Meeting Abstracts. 2012;120(21):309. Itzykson R, Kosmider O, Renneville A, Morabito M, Buet D, Preudhomme C, et al. Two distinct mechanisms contribute to granulomonocytic hyperplasia in chronic myelomonocytic Leukemias (CMML). ASH Annual Meeting Abstracts. 2012;120(21):309.
46.
go back to reference Madzo J, Liu H, Rodriguez A, Vasanthakumar A, Sundaravel S, Caces DB, et al. Hydroxymethylation at gene regulatory regions directs stem/early progenitor cell commitment during erythropoiesis. Cell Rep. 2014;6(1):231–44.CrossRefPubMed Madzo J, Liu H, Rodriguez A, Vasanthakumar A, Sundaravel S, Caces DB, et al. Hydroxymethylation at gene regulatory regions directs stem/early progenitor cell commitment during erythropoiesis. Cell Rep. 2014;6(1):231–44.CrossRefPubMed
47.
go back to reference Fuster JJ, MacLauchlan S, Zuriaga MA, Polackal MN, Ostriker AC, Chakraborty R, et al. Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice. Science. 2017;355(6327):842–7.CrossRefPubMed Fuster JJ, MacLauchlan S, Zuriaga MA, Polackal MN, Ostriker AC, Chakraborty R, et al. Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice. Science. 2017;355(6327):842–7.CrossRefPubMed
48.
go back to reference Carey A, Edwards DKT, Eide CA, Newell L, Traer E, Medeiros BC, et al. Identification of Interleukin-1 by functional screening as a key mediator of cellular expansion and disease progression in acute myeloid Leukemia. Cell Rep. 2017;18(13):3204–18.CrossRefPubMed Carey A, Edwards DKT, Eide CA, Newell L, Traer E, Medeiros BC, et al. Identification of Interleukin-1 by functional screening as a key mediator of cellular expansion and disease progression in acute myeloid Leukemia. Cell Rep. 2017;18(13):3204–18.CrossRefPubMed
49.
go back to reference El-Fattah MA. Clinical prognostic factors and survival outcome of chronic myelomonocytic leukemia: reviewing 3,686 patients. Clin Lymphoma Myeloma Leuk. 2016;16(8):e119–21.CrossRefPubMed El-Fattah MA. Clinical prognostic factors and survival outcome of chronic myelomonocytic leukemia: reviewing 3,686 patients. Clin Lymphoma Myeloma Leuk. 2016;16(8):e119–21.CrossRefPubMed
50.
go back to reference Worsley A, Oscier DG, Stevens J, Darlow S, Figes A, Mufti GJ, et al. Prognostic features of chronic myelomonocytic leukaemia: a modified Bournemouth score gives the best prediction of survival. Br J Haematol. 1988;68(1):17–21.CrossRefPubMed Worsley A, Oscier DG, Stevens J, Darlow S, Figes A, Mufti GJ, et al. Prognostic features of chronic myelomonocytic leukaemia: a modified Bournemouth score gives the best prediction of survival. Br J Haematol. 1988;68(1):17–21.CrossRefPubMed
51.
go back to reference Fenaux P, Beuscart R, Lai JL, Jouet JP, Bauters F. Prognostic factors in adult chronic myelomonocytic leukemia: an analysis of 107 cases. J Clin Oncol. 1988;6(9):1417–24.CrossRefPubMed Fenaux P, Beuscart R, Lai JL, Jouet JP, Bauters F. Prognostic factors in adult chronic myelomonocytic leukemia: an analysis of 107 cases. J Clin Oncol. 1988;6(9):1417–24.CrossRefPubMed
52.
go back to reference Onida F, Kantarjian HM, Smith TL, Ball G, Keating MJ, Estey EH, et al. Prognostic factors and scoring systems in chronic myelomonocytic leukemia: a retrospective analysis of 213 patients. Blood. 2002;99(3):840–9.CrossRefPubMed Onida F, Kantarjian HM, Smith TL, Ball G, Keating MJ, Estey EH, et al. Prognostic factors and scoring systems in chronic myelomonocytic leukemia: a retrospective analysis of 213 patients. Blood. 2002;99(3):840–9.CrossRefPubMed
53.
go back to reference Germing U, Kundgen A, Gattermann N. Risk assessment in chronic myelomonocytic leukemia (CMML). Leuk Lymphoma. 2004;45(7):1311–8.CrossRefPubMed Germing U, Kundgen A, Gattermann N. Risk assessment in chronic myelomonocytic leukemia (CMML). Leuk Lymphoma. 2004;45(7):1311–8.CrossRefPubMed
54.
go back to reference Wassie EA, Itzykson R, Lasho TL, Kosmider O, Finke CM, Hanson CA, et al. Molecular and prognostic correlates of cytogenetic abnormalities in chronic myelomonocytic leukemia: a Mayo Clinic-French Consortium Study. Am J Hematol. 2014;89(12):1111–5.CrossRefPubMed Wassie EA, Itzykson R, Lasho TL, Kosmider O, Finke CM, Hanson CA, et al. Molecular and prognostic correlates of cytogenetic abnormalities in chronic myelomonocytic leukemia: a Mayo Clinic-French Consortium Study. Am J Hematol. 2014;89(12):1111–5.CrossRefPubMed
55.
go back to reference Gelsi-Boyer V, Trouplin V, Roquain J, Adelaide J, Carbuccia N, Esterni B, et al. ASXL1 mutation is associated with poor prognosis and acute transformation in chronic myelomonocytic leukaemia. Br J Haematol. 2010;151(4):365–75.CrossRefPubMed Gelsi-Boyer V, Trouplin V, Roquain J, Adelaide J, Carbuccia N, Esterni B, et al. ASXL1 mutation is associated with poor prognosis and acute transformation in chronic myelomonocytic leukaemia. Br J Haematol. 2010;151(4):365–75.CrossRefPubMed
56.
go back to reference Patnaik MM, Itzykson R, Lasho TL, Kosmider O, Finke CM, Hanson CA, et al. ASXL1 and SETBP1 mutations and their prognostic contribution in chronic myelomonocytic leukemia: a two-center study of 466 patients. Leukemia. 2014;28(11):2206–12.CrossRefPubMed Patnaik MM, Itzykson R, Lasho TL, Kosmider O, Finke CM, Hanson CA, et al. ASXL1 and SETBP1 mutations and their prognostic contribution in chronic myelomonocytic leukemia: a two-center study of 466 patients. Leukemia. 2014;28(11):2206–12.CrossRefPubMed
57.
go back to reference Elena C, Galli A, Such E, Meggendorfer M, Germing U, Rizzo E, et al. Integrating clinical features and genetic lesions in the risk assessment of patients with chronic myelomonocytic leukemia. Blood. 2016;128(10):1408–17.CrossRefPubMedPubMedCentral Elena C, Galli A, Such E, Meggendorfer M, Germing U, Rizzo E, et al. Integrating clinical features and genetic lesions in the risk assessment of patients with chronic myelomonocytic leukemia. Blood. 2016;128(10):1408–17.CrossRefPubMedPubMedCentral
58.
go back to reference Patnaik MM, Zahid MF, Lasho TL, Finke C, Ketterling RL, Gangat N, et al. Number and type of TET2 mutations in chronic myelomonocytic leukemia and their clinical relevance. Blood Cancer J. 2016;6(9):e472.CrossRefPubMedPubMedCentral Patnaik MM, Zahid MF, Lasho TL, Finke C, Ketterling RL, Gangat N, et al. Number and type of TET2 mutations in chronic myelomonocytic leukemia and their clinical relevance. Blood Cancer J. 2016;6(9):e472.CrossRefPubMedPubMedCentral
59.
go back to reference Grossmann V, Kohlmann A, Eder C, Haferlach C, Kern W, Cross NC, et al. Molecular profiling of chronic myelomonocytic leukemia reveals diverse mutations in >80% of patients with TET2 and EZH2 being of high prognostic relevance. Leukemia. 2011;25(5):877–9.CrossRefPubMed Grossmann V, Kohlmann A, Eder C, Haferlach C, Kern W, Cross NC, et al. Molecular profiling of chronic myelomonocytic leukemia reveals diverse mutations in >80% of patients with TET2 and EZH2 being of high prognostic relevance. Leukemia. 2011;25(5):877–9.CrossRefPubMed
60.
go back to reference Patnaik MM, Barraco D, Lasho TL, Finke CM, Hanson CA, Ketterling RP, et al. DNMT3A mutations are associated with inferior overall and leukemia-free survival in chronic myelomonocytic leukemia. Am J Hematol. 2017;92(1):56–61.CrossRefPubMed Patnaik MM, Barraco D, Lasho TL, Finke CM, Hanson CA, Ketterling RP, et al. DNMT3A mutations are associated with inferior overall and leukemia-free survival in chronic myelomonocytic leukemia. Am J Hematol. 2017;92(1):56–61.CrossRefPubMed
61.
go back to reference Such E, Germing U, Malcovati L, Cervera J, Kuendgen A, Della Porta MG, et al. Development and validation of a prognostic scoring system for patients with chronic myelomonocytic leukemia. Blood. [Research Support, Non-U.S. Gov’t. Validation Studies]. 2013;121(15):3005–15. Such E, Germing U, Malcovati L, Cervera J, Kuendgen A, Della Porta MG, et al. Development and validation of a prognostic scoring system for patients with chronic myelomonocytic leukemia. Blood. [Research Support, Non-U.S. Gov’t. Validation Studies]. 2013;121(15):3005–15.
62.
go back to reference Patnaik MM, Padron E, Laborde RR, Lasho TL, Finke CM, Hanson CA, et al. Mayo prognostic model for WHO-defined chronic myelomonocytic leukemia: aSXL1 and spliceosome component mutations and outcomes. Leukemia. 2013;27(7):1504–10.CrossRefPubMed Patnaik MM, Padron E, Laborde RR, Lasho TL, Finke CM, Hanson CA, et al. Mayo prognostic model for WHO-defined chronic myelomonocytic leukemia: aSXL1 and spliceosome component mutations and outcomes. Leukemia. 2013;27(7):1504–10.CrossRefPubMed
63.
go back to reference Padron E, Garcia-Manero G, Patnaik MM, Itzykson R, Lasho T, Nazha A, et al. An international data set for CMML validates prognostic scoring systems and demonstrates a need for novel prognostication strategies. Blood Cancer J. 2015;5:e333.CrossRefPubMedPubMedCentral Padron E, Garcia-Manero G, Patnaik MM, Itzykson R, Lasho T, Nazha A, et al. An international data set for CMML validates prognostic scoring systems and demonstrates a need for novel prognostication strategies. Blood Cancer J. 2015;5:e333.CrossRefPubMedPubMedCentral
64.
go back to reference Yoshizato T, Nannya Y, Atsuta Y, Shiozawa Y, Iijima-Yamashita Y, Yoshida K, et al. Impact of genetic alterations in stem-cell transplantation for myelodysplasia and secondary acute myeloid leukemia. Blood. 2017 Feb 21. Yoshizato T, Nannya Y, Atsuta Y, Shiozawa Y, Iijima-Yamashita Y, Yoshida K, et al. Impact of genetic alterations in stem-cell transplantation for myelodysplasia and secondary acute myeloid leukemia. Blood. 2017 Feb 21.
65.
go back to reference Xicoy B, Germing U, Jimenez MJ, Garcia O, Garcia R, Schemenau J, et al. Response to erythropoietic-stimulating agents in patients with chronic myelomonocytic leukemia. Eur J Haematol. 2016;97(1):33–8.CrossRefPubMed Xicoy B, Germing U, Jimenez MJ, Garcia O, Garcia R, Schemenau J, et al. Response to erythropoietic-stimulating agents in patients with chronic myelomonocytic leukemia. Eur J Haematol. 2016;97(1):33–8.CrossRefPubMed
66.
go back to reference Ramadan H, Duong VH, Al Ali N, Padron E, Zhang L, Lancet JE, et al. Eltrombopag Use in Patients With Chronic Myelomonocytic Leukemia (CMML): a Cautionary Tale. Clin Lymphoma Myeloma Leuk. 2016;16(Suppl):S64–6.CrossRefPubMed Ramadan H, Duong VH, Al Ali N, Padron E, Zhang L, Lancet JE, et al. Eltrombopag Use in Patients With Chronic Myelomonocytic Leukemia (CMML): a Cautionary Tale. Clin Lymphoma Myeloma Leuk. 2016;16(Suppl):S64–6.CrossRefPubMed
67.
go back to reference de Witte T, Bowen D, Robin M, Malcovati L, Niederwieser D, Yakoub-Agha I, et al. Allogeneic hematopoietic stem cell transplantation for MDS and CMML: recommendations from an international expert panel. Blood. 2017;129(13):1753–62.CrossRefPubMed de Witte T, Bowen D, Robin M, Malcovati L, Niederwieser D, Yakoub-Agha I, et al. Allogeneic hematopoietic stem cell transplantation for MDS and CMML: recommendations from an international expert panel. Blood. 2017;129(13):1753–62.CrossRefPubMed
68.
go back to reference Kantarjian H, Beran M, Cortes J, O’Brien S, Giles F, Pierce S, et al. Long-term follow-up results of the combination of topotecan and cytarabine and other intensive chemotherapy regimens in myelodysplastic syndrome. Cancer. 2006;106(5):1099–109.CrossRefPubMed Kantarjian H, Beran M, Cortes J, O’Brien S, Giles F, Pierce S, et al. Long-term follow-up results of the combination of topotecan and cytarabine and other intensive chemotherapy regimens in myelodysplastic syndrome. Cancer. 2006;106(5):1099–109.CrossRefPubMed
69.
go back to reference Ades L, Sekeres MA, Wolfromm A, Teichman ML, Tiu RV, Itzykson R, et al. Predictive factors of response and survival among chronic myelomonocytic leukemia patients treated with azacitidine. Leuk Res. [Clinical Trial]. 2013 Jun;37(6):609-13. Ades L, Sekeres MA, Wolfromm A, Teichman ML, Tiu RV, Itzykson R, et al. Predictive factors of response and survival among chronic myelomonocytic leukemia patients treated with azacitidine. Leuk Res. [Clinical Trial]. 2013 Jun;37(6):609-13.
70.
go back to reference Alfonso A, Montalban-Bravo G, Takahashi K, Jabbour EJ, Kadia T, Ravandi F, et al. Natural history of chronic myelomonocytic leukemia treated with hypomethylating agents. Am J Hematol. 2017 Mar 28. Alfonso A, Montalban-Bravo G, Takahashi K, Jabbour EJ, Kadia T, Ravandi F, et al. Natural history of chronic myelomonocytic leukemia treated with hypomethylating agents. Am J Hematol. 2017 Mar 28.
71.
go back to reference Braun T, Itzykson R, Renneville A, de Renzis B, Dreyfus F, Laribi K, et al. Molecular predictors of response to decitabine in advanced chronic myelomonocytic leukemia: a phase II trial. Blood. 2011;9(118):3824–31.CrossRef Braun T, Itzykson R, Renneville A, de Renzis B, Dreyfus F, Laribi K, et al. Molecular predictors of response to decitabine in advanced chronic myelomonocytic leukemia: a phase II trial. Blood. 2011;9(118):3824–31.CrossRef
72.
go back to reference Meldi K, Qin T, Buchi F, Droin N, Sotzen J, Micol JB, et al. Specific molecular signatures predict decitabine response in chronic myelomonocytic leukemia. The Journal of clinical investigation. 2015 Mar 30. Meldi K, Qin T, Buchi F, Droin N, Sotzen J, Micol JB, et al. Specific molecular signatures predict decitabine response in chronic myelomonocytic leukemia. The Journal of clinical investigation. 2015 Mar 30.
73.
go back to reference Lee SC, Dvinge H, Kim E, Cho H, Micol JB, Chung YR, et al. Modulation of splicing catalysis for therapeutic targeting of leukemia with mutations in genes encoding spliceosomal proteins. Nat Med. 2016;22(6):672–8.CrossRefPubMedPubMedCentral Lee SC, Dvinge H, Kim E, Cho H, Micol JB, Chung YR, et al. Modulation of splicing catalysis for therapeutic targeting of leukemia with mutations in genes encoding spliceosomal proteins. Nat Med. 2016;22(6):672–8.CrossRefPubMedPubMedCentral
Metadata
Title
CMML: Clinical and molecular aspects
Authors
Raphael Itzykson
Matthieu Duchmann
Nolwenn Lucas
Eric Solary
Publication date
01-06-2017
Publisher
Springer Japan
Published in
International Journal of Hematology / Issue 6/2017
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-017-2243-z

Other articles of this Issue 6/2017

International Journal of Hematology 6/2017 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine