[Reviews] Pathogenetic and clinical significance of genetic abnormalities in acute myeloid leukemia

概要

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[Abstract] Acute myeloid leukemia (AML) is a clonal disorder that is caused by acquired somatic mutations in hematopoietic stem/progenitors. These mutations mainly include chromosomal translocations and point mutations, which were divided into two major groups called Class I and Class II mutations. Class I mutations including those of FLT3, KIT, and RAS, which primarily promote the growth and survival of hematopoietic cells without significant effects on differentiation. Class II mutations include those of CBF, RARA, CEBPA, and MLL, which cause differentiation arrest or are involved in self-renewal of hematopoietic cells, while they hardly affect the growth and survival of hematopoietic cells. Thus, the cooperation between class I mutation and class II mutation is supposed to be required to develop AML. The screening of these genetic mutations is now performed to diagnose AML in daily clinical practice. In addition, because these abnormalities crucially influence biologic properties of AML cells, they are the most important prognostic factors for AML and utilized to classify AML in the WHO classification. Furthermore, recent advances in the understanding of the genetic basis have enabled us to construct novel therapeutic approaches, and some of which are already in clinical trials or applied to daily clinical practice.