Combined mutations of ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, RUNX1, TET2 and WT1 genes in myelodysplastic syndromes and acute myeloid leukemias

BMC Cancer

Research Article

Virginie Trouplin¹  Daniel Birnbaum¹  Julien Rocquain¹  Nadine Carbuccia¹  Stéphane Raynaud¹  Marie-Joelle Mozziconacci²  Anne Murati²  Sylviane Olschwang²  Véronique Gelsi-Boyer³  Norbert Vey⁴  Meyer Nezri⁵  Zoulika Tadrist⁶ 

[1] Centre de Recherche en Cancérologie de Marseille, Laboratoire d'Oncologie Moléculaire; UMR891 Inserm; Institut Paoli-Calmettes, Marseille, France;Centre de Recherche en Cancérologie de Marseille, Laboratoire d'Oncologie Moléculaire; UMR891 Inserm; Institut Paoli-Calmettes, Marseille, France;Département de BioPathologie, Institut Paoli-Calmettes, Marseille, France;Centre de Recherche en Cancérologie de Marseille, Laboratoire d'Oncologie Moléculaire; UMR891 Inserm; Institut Paoli-Calmettes, Marseille, France;Département de BioPathologie, Institut Paoli-Calmettes, Marseille, France;Faculté de Médecine, Université de la Méditerranée, Marseille, France;Faculté de Médecine, Université de la Méditerranée, Marseille, France;Département d'Hématologie, Institut Paoli-Calmettes, Marseille, France;Service de Médecine Interne, Centre Hospitalier Général, Martigues, France;Service de Médecine Interne-Oncologie, Hôpital de Salon-de-Provence, Salon-de-Provence, France;

关键词: Acute Myeloid Leukemia;    JAK2 V617F;    Balance Translocation;    Internal Tandem Duplication;    Myeloid Malignancy;   

DOI  :  10.1186/1471-2407-10-401

 received in 2010-02-22, accepted in 2010-08-02,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundGene mutation is an important mechanism of myeloid leukemogenesis. However, the number and combination of gene mutated in myeloid malignancies is still a matter of investigation.MethodsWe searched for mutations in the ASXL1, CBL, FLT3, IDH1, IDH2, JAK2, KRAS, NPM1, NRAS, RUNX1, TET2 and WT1 genes in 65 myelodysplastic syndromes (MDSs) and 64 acute myeloid leukemias (AMLs) without balanced translocation or complex karyotype.ResultsMutations in ASXL1 and CBL were frequent in refractory anemia with excess of blasts. Mutations in TET2 occurred with similar frequency in MDSs and AMLs and associated equally with either ASXL1 or NPM1 mutations. Mutations of RUNX1 were mutually exclusive with TET2 and combined with ASXL1 but not with NPM1. Mutations in FLT3 (mutation and internal tandem duplication), IDH1, IDH2, NPM1 and WT1 occurred primarily in AMLs.ConclusionOnly 14% MDSs but half AMLs had at least two mutations in the genes studied. Based on the observed combinations and exclusions we classified the 12 genes into four classes and propose a highly speculative model that at least a mutation in one of each class is necessary for developing AML with simple or normal karyotype.

【 授权许可】

Unknown   
© Rocquain et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.