Molecular biology of acute myeloid leukemia

Clonal chromosome translocations, deletions, and inversions have been repeatedly observed for decades in approximately two thirds of all cases of acute myeloid leukemia (AML). With the dramatic advances in molecular biology that have occurred during the past two decades, these structural cytogenetic abnormalities have now provided invaluable clues as to the location of genes known or suspected of inducing leukemia. In most instances, leukemogenesis in AML results from gene fusion, when segments from two different genes are fused together to give rise to a chimeric structure consisting of the 5' end of one gene and the 3' end of another. Exceptions to this, however, do exist. In cases of AML that lack cytogenetic abnormalities, investigators are now also beginning to elucidate the genes involved in malignant transformation. Together, these observations support the notion that AML is heterogeneous at the molecular level, and suggest that clinicians will need to continue to take cytogenetic and molecular characteristics into consideration to optimize patient therapy.