Epigenesis in acute myeloid leukemia: an update

Acute myeloid leukemia (AML) is a hematological malignancy characterized by uncontrolled proliferation of clonal neoplastic hematopoietic precursor cells leading to the disruption of normal hematopoiesis and bone marrow failure. While about 45% of AML cases show a normal karyotype with mutations detectable only at the molecular level, 55% display chromosomal rearrangements including deletions, insertions, segmental and complete monosomy/trisomy, and gene fusions created by translocations. However, AML is not induced by cytogenetic abnormalities and gene mutations alone: the current body of literature implicates abnormal epigenetics-specifically, abnormal levels of DNA methylation, chemical modification of histones, and non-coding RNA expression-in the flawed regulation of the fundamental genes of hematopoiesis. Those three mechanisms may deviate the myeloid lineage from a healthy hematopoiesis to, instead, leukemogenesis.