Top

Published in:

Open Access 01-12-2014 | Review

Molecular genetics of chronic neutrophilic leukemia, chronic myelomonocytic leukemia and atypical chronic myeloid leukemia

Authors: Bing Li, Robert Peter Gale, Zhijian Xiao

Published in: Journal of Hematology & Oncology | Issue 1/2014

Abstract

According to the 2008 World Health Organization classification, chronic neutrophilic leukemia, chronic myelomonocytic leukemia and atypical chronic myeloid leukemia are rare diseases. The remarkable progress in our understanding of the molecular genetics of myeloproliferative neoplasms and myelodysplastic/myeloproliferative neoplasms has made it clear that there are some specific genetic abnormalities in these 3 rare diseases. At the same time, there is considerable overlap among these disorders at the molecular level. The various combinations of genetic abnormalities indicate a multi-step pathogenesis, which likely contributes to the marked clinical heterogeneity of these disorders. This review focuses on the current knowledge and challenges related to the molecular pathogenesis of chronic neutrophilic leukemia, chronic myelomonocytic leukemia and atypical chronic myeloid leukemia and relationships between molecular findings, clinical features and prognosis.

Available only for authorised users

Maxson JE, Gotlib J, Pollyea DA, Fleischman AG, Agarwal A, Eide CA, Bottomly D, Wilmot B, McWeeney SK, Tognon CE, Pond JB, Collins RH, Goueli B, Oh ST, Deininger MW, Chang BH, Loriaux MM, Druker BJ, Tyner JW: Oncogenic CSF3R mutations in chronic neutrophilic leukemia and atypical CML. N Engl J Med. 2013, 368: 1781-1790. 10.1056/NEJMoa1214514.PubMedCentralCrossRefPubMed

Dong F, van Buitenen C, Pouwels K, Hoefsloot LH, Lowenberg B, Touw IP: Distinct cytoplasmic regions of the human granulocyte colony-stimulating factor receptor involved in induction of proliferation and maturation. Mol Cell Biol. 1993, 13: 7774-7781.PubMedCentralCrossRefPubMed

Fleischman AG, Maxson JE, Luty SB, Agarwal A, Royer LR, Abel ML, MacManiman JD, Loriaux MM, Druker BJ, Tyner JW: The CSF3R T618I mutation causes a lethal neutrophilic neoplasia in mice that is responsive to therapeutic JAK inhibition. Blood. 2013, 122: 3628-3631. 10.1182/blood-2013-06-509976.PubMedCentralCrossRefPubMed

Pardanani A, Lasho TL, Laborde RR, Elliott M, Hanson CA, Knudson RA, Ketterling RP, Maxson JE, Tyner JW, Tefferi A: CSF3R T618I is a highly prevalent and specific mutation in chronic neutrophilic leukemia. Leukemia. 2013, 27: 1870-1873. 10.1038/leu.2013.122.PubMedCentralCrossRefPubMed

Ito T, Kojima H, Otani K, Komeno T, Mitsuhashi S, Hasegawa Y, Kobayashi T, Ninomiya H, Nagasawa T, Abe T: Chronic neutrophilic leukemia associated with monoclonal gammopathy of undetermined significance. Acta Haematol. 1996, 95: 140-143. 10.1159/000203863.CrossRefPubMed

Rovira M, Cervantes F, Nomdedeu B, Rozman C: Chronic neutrophilic leukaemia preceding for seven years the development of multiple myeloma. Acta Haematol. 1990, 83: 94-95. 10.1159/000205176.CrossRefPubMed

Kohmura K, Miyakawa Y, Kameyama K, Kizaki M, Ikeda Y: Granulocyte colony stimulating factor-producing multiple myeloma associated with neutrophilia. Leuk Lymphoma. 2004, 45: 1475-1479. 10.1080/10428190310001645870.CrossRefPubMed

Standen GR, Steers FJ, Jones L: Clonality of chronic neutrophilic leukaemia associated with myeloma: analysis using the X-linked probe M27 beta. J Clin Pathol. 1993, 46: 297-298. 10.1136/jcp.46.4.297.PubMedCentralCrossRefPubMed

Cui Y, Li B, Gale RP, Jiang Q, Xu Z, Qin T, Zhang P, Zhang Y, Xiao Z: CSF3R, SETBP1 and CALR mutations in chronic neutrophilic leukemia. J Hematol Oncol. 2014, 7: 77-10.1186/s13045-014-0077-1.PubMedCentralCrossRefPubMed

10.

Levine R, Loriaux M, Huntly BJ, Loh ML, Beran M, Stoffregen E, Berger R, Clark JJ, Willis SG, Nguyen KT, Flores NJ, Estey E, Gattermann N, Armstrong S, Look AT, Griffin JD, Bernard OA, Heinrich MC, Gilliland DG, Druker B, Deininger MW: The JAK2V617F activating mutation occurs in chronic myelomonocytic leukemia and acute myeloid leukemia, but not in acute lymphoblastic leukemia or chronic lymphocytic leukemia. Blood. 2005, 106: 3377-3379. 10.1182/blood-2005-05-1898.PubMedCentralCrossRefPubMed

11.

Pastore F, Schneider S, Christ O, Hiddemann W, Spiekermann K: Impressive thrombocytosis evolving in a patient with a BCR-ABL positive CML in major molecular response during dasatinib treatment unmasks an additional JAK2V617F. Exp Hematol Oncol. 2013, 2: 24-10.1186/2162-3619-2-24.PubMedCentralCrossRefPubMed

12.

Ortiz-Cruz K, Amog-Jones G, Salvatore JR: Chronic neutrophilic leukemiawith JAK2 gene mutation. Commun Oncol. 2012, 9: 127-131. 10.1016/j.cmonc.2012.03.012.CrossRef

13.

Mc Lornan DP, Percy MJ, Jones AV, Cross NC, Mc Mullin MF: Chronic neutrophilic leukemia with an associated V617F JAK2 tyrosine kinase mutation. Haematologica. 2005, 90: 1696-1697.PubMed

14.

Lee J-H, Ha JS, Ryoo NH, Jeon DS, Kim JR: A case of acute myeloid leukemia transformed from JAK2 V617F-positive chronic neutrophilic leukemia. Lab Med Online. 2012, 2: 101-104. 10.3343/lmo.2012.2.2.101.CrossRef

15.

Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, Them NC, Berg T, Gisslinger B, Pietra D, Chen D, Vladimer GI, Bagienski K, Milanesi C, Casetti IC, Sant’Antonio E, Ferretti V, Elena C, Schischlik F, Cleary C, Six M, Schalling M, Schonegger A, Bock C, Malcovati L, Pascutto C, Superti-Furga G, Cazzola M, Kralovics R: Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med. 2013, 369: 2379-2390. 10.1056/NEJMoa1311347.CrossRefPubMed

16.

Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC, Avezov E, Li J, Kollmann K, Kent DG, Aziz A, Godfrey AL, Hinton J, Martincorenal I, Van Loo P, Jones AV, Guglielmelli P, Tarpey P, Harding HP, Fitzpatrick JD, Goudie CT, Ortmann CA, Loughran SJ, Raine K, Jones DR, Butler AP, Teague JW, O’Meara S, McLaren S, Bianchi M: Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med. 2013, 369: 2391-2405. 10.1056/NEJMoa1312542.PubMedCentralCrossRefPubMed

17.

Rotunno G, Mannarelli C, Guglielmelli P, Pacilli A, Pancrazzi A, Pieri L, Fanelli T, Bosi A, Vannucchi AM: Associazione Italiana per la Ricerca sul Cancro Gruppo Italiano Malattie Mieloproliferative Investigators. Impact fo calreticulin mutations on clinical and hematological phenotype and outcome in essential thrombocythemia. Blood. 2014, 123: 1552-1555. 10.1182/blood-2013-11-538983.CrossRefPubMed

18.

Tefferi A, Lasho TL, Finke CM, Finke CM, Knudson RA, Ketterling R, Hanson CH, Maffioli M, Caramazza D, Passamonti F, Pardanani A: CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons. Leukemia. 2014, 28: 1472-1477. 10.1038/leu.2014.3.CrossRefPubMed

19.

Gajendra S, Gupta R, Chandgothia M, Kumar L, Gupta R, Chavan SM: Chronic neutrophilic leukemia with V617F JAK2 mutation. Indian J Hematol Blood Transfus. 2014, 30: 139-142. 10.1007/s12288-012-0203-6.PubMedCentralCrossRefPubMed

20.

Lasho TL, Elliott MA, Pardanani A, Tefferi A: CALR mutation studies in chronic neutrophilic leukemia. Am J Hematol. 2014, 89: 450-10.1002/ajh.23665.CrossRefPubMed

21.

Piazza R, Valletta S, Winkelmann N, Winkelmann N, Redaelli S, Spinelli R, Pirola A, Antolini L, Mologni L, Donadoni C, Papaemmanuil E, Schnittger S, Kim DW, Boultwood J, Rossi F, Gaipa G, De Martini GP, di Celle PF, Jang HG, Fantin V, Bignell GR, Magistroni V, Haferlach T, Pogliani EM, Campbell PJ, Chase AJ, Tapper WJ, Cross NC, Gambacorti-Passerini C: Recurrent SETBP1 mutations in atypical chronic myeloid leukemia. Nat Genet. 2013, 45: 18-24. 10.1038/ng.2495.PubMedCentralCrossRefPubMed

22.

Lasho TL, Mims A, Elliott MA, Finke C, Pardanani A, Tefferi A: Chronic neutrophilic leukemia with concurrent CSF3R and SETBP1 mutations: single colony clonality studies, in vitro sensitivity to JAK inhibitors and lack of treatment response to ruxolitinib. Leukemia. 2014, 28: 1363-1365. 10.1038/leu.2014.39.CrossRefPubMed

23.

Gelsi-Boyer V, Brecqueville M, Devillier R, Murati A, Mozziconacci MJ, Birnbaum D: Mutations in ASXL1 are associated with poor prognosis across the spectrum of malignant myeloid diseases. J Hematol Oncol. 2012, 5: 12-10.1186/1756-8722-5-12.PubMedCentralCrossRefPubMed

24.

Itzykson R, Kosmider O, Renneville A, Gelsi-Boyer V, Meggendorfer M, Morabito M, Berthon C, Ades L, Fenaux P, Beyne-Rauzy O, Vey N, Braun T, Haferlach T, Dreyfus F, Cross NC, Preudhomme C, Bernard OA, Fontenay M, Vainchenker W, Schnittger S, Birnbaum D, Droin N, Solary E: Prognostic score including gene mutations in chronic myelomonocytic leukemia. J Clin Oncol. 2013, 31: 2428-2436. 10.1200/JCO.2012.47.3314.CrossRefPubMed

25.

Itzykson R, Kosmider O, Renneville A, Morabito M, Preudhomme C, Berthon C, Ades L, Fenaux P, Platzbecker U, Gagey O, Rameau P, Meurice G, Orear C, Delhommeau F, Bernard OA, Fontenay M, Vainchenker W, Droin N, Solary E: Clonal architecture of chronic myelomonocytic leukemias. Blood. 2013, 121: 2186-2198. 10.1182/blood-2012-06-440347.CrossRefPubMed

26.

Jankowska AM, Makishima H, Tiu RV, Szpurka H, Huang Y, Traina F, Visconte V, Sugimoto Y, Prince C, O’Keefe C, His ED, List A, Sekeres MA, Rao A, McDevitt MA, Maciejewski JP: Mutational spectrum analysis of chronic myelomonocytic leukemia includes gene associated with epigenetic regulation: UTX, EZH2, and DNMT3A. Blood. 2011, 118: 3932-3941. 10.1182/blood-2010-10-311019.PubMedCentralCrossRefPubMed

27.

Yoshida K, Sanada M, Shiraishi Y, Nowak D, Nagata Y, Yamamoto R, Sato Y, Sato-Otsubo A, Kon A, Nagasaki M, Chalkidis G, Suzuki Y, Shiosaka M, Kawahata R, Yamaguchi T, Otsu M, Obara N, Sakata-Yanagimoto M, Ishiyama K, Mori H, Nolte F, Hofmann WK, Miyawaki S, Sugano S, Haferlach C, Koeffler HP, Shih LY, Haferlach T, Chiba S, Nakauchi H: Frequent pathway mutations of splicing machinery in myelodysplasia. Nature. 2011, 478: 64-69. 10.1038/nature10496.CrossRefPubMed

28.

Meggendorfer M, Roller A, Haferlach T, Eder C, Dicker F, Grossmann V, Kohlmann A, Alpermann T, Yoshida K, Ogawa S, Koeffler HP, Kern W, Haferlach C, Schnittger S: SRSF2 mutations in 275 cases with chronic myelomonocytic leukemia (CMML). Blood. 2012, 120: 3080-3088. 10.1182/blood-2012-01-404863.PubMedCentralCrossRefPubMed

29.

Kar SA, Jankowska A, Makishima H, Visconte V, Jerez A, Sugimotto Y, Muramatsu H, Traina F, Afable M, Guinta K, Tiu RV, Przychodzen B, Sakaguchi H, Kojima S, Sekeres MA, List AF, McDevitt MA, Maciejewski JP: Spliceosomal gene mutations are frequent events in the diverse mutational spectrum of chronic myelomonocytic leukemia but largely absent in juvenile myelomonocytic leukemia. Haematologica. 2013, 98: 107-113. 10.3324/haematol.2012.064048.PubMedCentralCrossRefPubMed

30.

Patnaik MM, Padron E, LaBorde RR, Lasho TL, Finke CM, Hanson CA, Hodnefield JM, Knudson RA, Ketterling RP, Al-kali A, Pardanani A, Ali NA, Komrokji RS, Tefferi A: Mayo prognostic model for WHO-defined chronic myelomonocytic leukemia: ASXL1 and spliceosome component mutations and outcomes. Leukemia. 2013, 27: 1504-1510. 10.1038/leu.2013.88.CrossRefPubMed

31.

Kuo MC, Liang DC, Huang CF, Shih YS, Wu JH, Lin TL, Shih LY: RUNX1 mutations are frequent in chronic myelomonocytic leukemia and mutations at the C-terminal region might predict acute myeloid leukemia transformation. Leukemia. 2009, 23: 1426-1431. 10.1038/leu.2009.48.CrossRefPubMed

32.

Gelsi-Boyer V, Trouplin V, Adelaide J, Aceto N, Remy V, Pinson S, Houdayer C, Arnoulet C, Sainty D, Bentires-Alj M, Olschwang S, Vey N, Mozziconacci MJ, Birnbaum D, Chaffanet M: Genome profiling of chronic myelomonocytic leukemia: frequent alterations of RAS and RUNX1 genes. BMC Cancer. 2008, 8: 299-10.1186/1471-2407-8-299.PubMedCentralCrossRefPubMed

33.

Ernst T, Chase A, Zoi K, Waghorn K, Hidalgo-Curtis C, Score J, Jones A, Grand F, Reiter A, Hochhaus A, Cross NC: Transcription factor mutations in myelodysplastic/myeloproliferative neoplasms. Haematologica. 2010, 95: 1473-1480. 10.3324/haematol.2010.021808.PubMedCentralCrossRefPubMed

34.

Kohlmann A, Grossmann V, Klein H, Schindela S, Weiss T, Kazak B, Dicker F, Schnittger S, Dugas M, Kern W, Haferlach C, Haferlach T: Next-generation sequencing technology reveals a characteristic pattern of molecular mutations in 72.8% of chronic myelomonocytic leukemia by detecting frequent alterations in TET2, CBL, RAS, and RUNX1. J Clin Oncol. 2010, 28: 3858-3865. 10.1200/JCO.2009.27.1361.CrossRefPubMed

35.

Kosmider O, Itzykson R, Chesnais V, Lasho T, Laborde R, Knudson R, Gauthier A, Merlevede J, Ades L, Morabito M, Fontenay M, Tefferi A, Droin N, Solary E: Mutations of the colony-stimulating factor-3 receptor gene is a rare event with poor prognosis in chronic myelomonocytic leukemia. Leukemia. 2013, 27: 1946-1949. 10.1038/leu.2013.182.CrossRefPubMed

36.

Damm F, Itzykson R, Kosmider O, Droin N, Renneville A, Chesnais V, Gelsi-Boyer V, de Botton S, Vey N, Preudhomme C, Clavert A, Delabesse E, Park S, Birnbaum D, Fontenay M, Bernard OA, Solary E: SETBP1 mutations in 658 patients with myelodysplastic syndromes, chronic myelomonocytic leukemia and secondary acute myeloid leukemias. Leukemia. 2013, 27: 1401-1403. 10.1038/leu.2013.35.CrossRefPubMed

37.

Laborde RR, Patnaik MM, Lasho TL, Finke CM, Hanson CA, Knudson RA, Ketterling RP, Pardanani A, Tefferi A: SETBP1 mutations in 415 patients with primary myelofibrosis or chronic myelomonocytic leukemia: independent prognostic impact in CMML. Leukemia. 2013, 27: 2100-2102. 10.1038/leu.2013.97.PubMedCentralCrossRefPubMed

38.

Kosmider O, Gelsi-Boyer V, Ciudad M, Racoeur C, Jooste V, Vey N, Quesnel B, Fenaux P, Bastie JN, Beyne-Rauzy O, Stamatoulas A, Dreyfus F, Ifrah N, de Botton S, Vainchenker W, Bernard OA, Birnbaum D, Fontenay M, Solary E: Groupe Francophone des Myelodysplasies. TET2 gene mutations is a frequent and adverse event in chronic myelomonocytic leukemia. Haematologica. 2009, 94: 1676-1681. 10.3324/haematol.2009.011205.PubMedCentralCrossRefPubMed

39.

Tefferi A, Lim KH, Abdel-Wahab O, Lasho TL, Patel J, Patnaik MM, Hanson CA, Pardanani A, Gilliland DG, Levine RL: Detection of mutant TET2 in myeloid malignancies other than myeloproliferative neoplasms: CMML, MDS, MDS/MPN and AML. Leukemia. 2009, 23: 1343-1345. 10.1038/leu.2009.59.PubMedCentralCrossRefPubMed

40.

Abdel-Wahab O, Pardanani A, Rampal R, Lasho RL, Tefferi A: DNMT3A mutational analysis in primary myelofibrosis, chronic myelomonocytic leukemia and advanced phases of myeloproliferative neoplasms. Leukemia. 2011, 25: 1219-1220. 10.1038/leu.2011.82.PubMedCentralCrossRefPubMed

41.

Gelsi-Boyer V, Trouplin V, Adelaide J, Bonansea J, Cervera N, Carbuccia N, Lagarde A, Prebet T, Nezri M, Sainty D, Olschwang S, Xerri L, Chaffanet M, Mozziconacci MJ, Vey N, Birnbaum D: Mutations of polycomb-associated gene ASXL1 in myelodysplastic syndromes and chronic myelomonocytic leukaemia. Br J Haematol. 2009, 145: 788-800. 10.1111/j.1365-2141.2009.07697.x.CrossRefPubMed

42.

Patanaik MM, Lasho TL, Finke CM, Hanson CA, Hodnefield JM, Knudson RA, Ketterling RP, Pardanani A, Tefferi A: Spliceosome mutations involving SRSF2, SF3B1, and U2AF35 in chronic myelomonocytic leukemia: prevalence, clinical correlates, and prognostic relevance. Am J Hematol. 2013, 88: 201-206. 10.1002/ajh.23373.CrossRef

43.

Malcovati L, Papaemmanuil E, Ambaglio I, Elena C, Galli A, Della Porta MG, Travaglino E, Pietra D, Pascutto C, Ubezio M, Bono E, Davia MC, Brisci A, Bruno F, Cremonesi L, Ferrari M, Boveri E, Invernizzi R, Campbell PJ, Cazzola M: Driver somatic mutations identify distinct disease entities within myeloid neoplasms with myelodysplasia. Blood. 2014, 124: 1513-1521. 10.1182/blood-2014-03-560227.PubMedCentralCrossRefPubMed

44.

Makishima H, Cazzolli H, Szpurka H, Dunbar A, Tiu R, Huh J, Muramatsu H, O’Keefe C, His E, Paquette RL, Kojima S, List AF, Sekeres MA, McDevitt MA, Maciejewski JP: Mutations of e3 ubiquitin ligase cbl family members constitute a novel common pathogenic lesion in myeloid malignancies. J Clin Oncol. 2009, 27: 6109-6116. 10.1200/JCO.2009.23.7503.PubMedCentralCrossRefPubMed

45.

Sanada M, Suzuki T, Shih LY, Otsu M, Kato M, Yamazaki S, Tamura A, Honda H, Sakata-Yanagimotto M, Kumano K, Oda H, Yamagata T, Takita J, Gotoh N, Nakazaki K, Kawamata N, Onodera M, Nobuyoshi M, Hayashi Y, Harada H, Kurokawa M, Chiba S, Mori H, Ozawa K, Omine M, Hirai H, Nakauchi H, Koeffler HP, Ogawa S: Gain-of-function of mutated C-CBL tumor suppressor in myeloid neoplasms. Nature. 2009, 460: 904-908. 10.1038/nature08240.CrossRefPubMed

46.

Beer PA, Delhommeau F, Lecouedic JP, Dawson MA, Chen E, Bareford D, Kusec R, McMullin MF, Harrison CN, Vannucchi AM, Vainchenker W, Green AR: Two routes to leukemic transformation after a JAK2 mutation-positive myeloproliferative neoplasm. Blood. 2010, 115: 2891-2900. 10.1182/blood-2009-08-236596.CrossRefPubMed

47.

Ferrer-Marin F, Bellosillo B, Martinez-Aviles L, Soler G, Carbonell P, Luengo-Gil G, Caparros E, Torregrosa JM, Besses C, Vicente V: Leukemic transformation driven by an ASXL1 mutation after a JAK2V617F-positive primary myelofibrosis: clonal evolution and hierarchy revealed by next-generation sequencing. J Hematol Oncol. 2013, 6: 68-10.1186/1756-8722-6-68.PubMedCentralCrossRefPubMed

48.

Meggendorfer M, Bacher U, Alpermann T, Haferlach C, Kern W, Gambacorti-Passerini C, Haferlach T, Schnittger S: SETBP1 mutations occur in 9% of MDS/MPN and in 4% of MPN cases and are strongly associated with atypical CML, monosomy 7, isochromosome i(17)(q10), ASXL1 and CBL mutations. Leukemia. 2013, 27: 1852-1860. 10.1038/leu.2013.133.CrossRefPubMed

49.

Albano F, Anelli L, Zagaria A, Coccaro N, Casieri P, Minervini A, Specchia G: SETBP1 and miR-4319 dysregulation in primary myelofibrosis progression to acute myeloid leukemia. J Hematol Oncol. 2012, 5: 48-10.1186/1756-8722-5-48.PubMedCentralCrossRefPubMed

50.

Jankowska AM, Szpurka H, Tiu RV, Makishima H, Afable M, Huh J, O’Keefe CL, Ganetzky R, McDevitt MA, Maciejewski JP: Loss of heterozygosity 4q24 and TET2 mutations associated with myelodysplastic/myeloproliferative neoplasms. Blood. 2009, 113: 6403-6410. 10.1182/blood-2009-02-205690.PubMedCentralCrossRefPubMed

51.

Meggendorfer M, Haferlach T, Alpermann T, Jeromin S, Haferlach C, Kern W, Schnittger S: Specific molecular mutation patterns delineate chronic neutrophilic leukemia, atypical chronic myeloid leukemia, and chronic myelomonocytic leukemia.Haematologica 2014, 113159. in press.,

52.

Tibes R, Mesa RA: Targeting hedgehog signaling in myelofibrosis and other hematologic malignancies. J Hematol Oncol. 2014, 7: 18-10.1186/1756-8722-7-18.PubMedCentralCrossRefPubMed

Title: Molecular genetics of chronic neutrophilic leukemia, chronic myelomonocytic leukemia and atypical chronic myeloid leukemia
Authors: Bing Li
Robert Peter Gale
Zhijian Xiao
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Journal of Hematology & Oncology / Issue 1/2014
Electronic ISSN: 1756-8722
DOI: https://doi.org/10.1186/s13045-014-0093-1

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

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

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2014

8q24 amplified segments involve novel fusion genes between NSMCE2 and long noncoding RNAs in acute myelogenous leukemia

Host bone marrow-derived IL-12 enhances donor T cell engraftment in a mouse model of bone marrow transplantation

Phase 1 trial of the oral AKT inhibitor MK-2206 plus carboplatin/paclitaxel, docetaxel, or erlotinib in patients with advanced solid tumors

Notch signaling and EMT in non-small cell lung cancer: biological significance and therapeutic application

Intratumoral anti-HuD immunotoxin therapy for small cell lung cancer and neuroblastoma

Pim kinases in hematological malignancies: where are we now and where are we going?

Keynote webinar | Spotlight on antibody–drug conjugates in cancer