Genetic basis of acute myeloid leukemia (AML): The most common molecular changes in patients with normal karyotype

Abstract Acute myeloid leukemia (AML) is a clonal disorder that results from errors in proliferation and differentiation of bone marrow stem cells from myeloid lineage. According to the Gilliland “two-hit” model, genes of both groups related to proliferation (e.g., FLT3) and differentiation (e.g., CEBPA) must be mutated for full development of AML. The genetic background of AML is very complicated and varied, from single nucleotide mutations or changes in gene expression to cytogenetic aberrations. The DNA sequencing results enable identification of important gene alterations that occur first and may lead the whole leukemogenesis (driver mutations). Some of them have prognostic significance – that is, they are related to the overall survival (OS), complete remission rate, and event-free survival (EFS). The most common molecular changes in AML are mutations in NPM1, CEBPA, FLT3, and DNMT3A. Alterations in NPM1 gene are associated with a good prognosis but simultaneous mutation in FLT3 may change this prognosis. DNMT3A mutations are very often correlated with NPM1 mutations and are associated with short OS.