Open Access Highly Accessed Research article

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

Julien Rocquain1, Nadine Carbuccia1, Virginie Trouplin1, Stéphane Raynaud1, Anne Murati12, Meyer Nezri3, Zoulika Tadrist4, Sylviane Olschwang12, Norbert Vey56, Daniel Birnbaum1, Véronique Gelsi-Boyer125 and Marie-Joelle Mozziconacci12*

Author Affiliations

1 Centre de Recherche en Cancérologie de Marseille; Laboratoire d'Oncologie Moléculaire; UMR891 Inserm; Institut Paoli-Calmettes; Marseille, France

2 Département de BioPathologie, Institut Paoli-Calmettes, Marseille, France

3 Service de Médecine Interne, Centre Hospitalier Général, Martigues, France

4 Service de Médecine Interne-Oncologie, Hôpital de Salon-de-Provence, Salon-de-Provence, France

5 Faculté de Médecine, Université de la Méditerranée, Marseille, France

6 Département d'Hématologie, Institut Paoli-Calmettes, Marseille, France

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BMC Cancer 2010, 10:401  doi:10.1186/1471-2407-10-401

Published: 2 August 2010



Gene 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.


We 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.


Mutations 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.


Only 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.