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Background  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.    Methods  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.    Results  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.    Conclusion  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.

bmc cancer

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