Molecular Genetics of Acute Myeloid Leukemia

Acute myeloid leukemia (AM L) is categorized by an increase in the number of myeloid cells in the marro w and an arrest in their maturation, frequently resulting in hematopoietic insufficiency. A co mmon theme in acute myeloid leu- kaemia (AML) associated with balanced reciprocal translocations is the involvement of transcription factors as one or both of the fusion partners. Transcription factors common ly involved in chro mosomal translocations include core bind ing factor (CBF), retinoic acid receptor alpha (RA Rα), mutations of the NPM1, FLT3, and CEBPA genes. The panel of known mo- lecular markers is continuously increasing, for example, considering the recently described TET2 and IDH1 mutations. Monitoring of the min imal residual disease load with quantitative real-t ime PCR can be performed for NPM 1 and other mutation cases. In addition, the recruitment of transcriptional co-activators and co-repressors by these transcription factors suggests that these proteins also may play a critical role in leukaemogenesis. CBP and p300 have been recently cloned. Treat ment for patients younger than 60 years consists of cytotoxic and might cure 20-75%, depending primarily on leu kemia cell cytogenetics. However, chemotherapy produces such a result in less than 10% o f elderly patients because of their inability to survive treat ment and, main ly, the association of old age with cytogenetic abnormalities in- volving chromosomes 5 and 7.The introduction of next generation sequencing will certainly cataly ze the molecu lar charac- terization of AM L.