Advances in molecular genetics and treatment of core-binding factor acute myeloid leukemia

Purpose of review Core-binding factor (CBF) acute myeloid leukemia (AML) is among the most common cytogenetic subtypes of AML, being detected in approximately 13% of adults with primary disease. Although CBF-AML is associated with a relatively favorable prognosis, only one-half of the patients are cured. Herein we review recent discoveries of genetic and epigenetic alterations in CBF-AML that may represent novel prognostic markers and therapeutic targets and lead to improvement of the still disappointing clinical outcome of these patients. Recent findings Several acquired gene mutations and gene-expression and microRNA-expression changes that occur in addition to t(8;21)(q22;q22) and inv(16)(p13q22)/t(16;16)(p13;q22), the cytogenetic hallmarks of CBF-AML, have been recently reported. Alterations that may represent cooperative events in CBF-AML leukemogenesis include mutations in the KIT, FLT3, JAK2 and RAS genes, haploinsufficiency of the putative tumor suppressor genes TLE1 and TLE4 in t(8;21)-positive patients with del(9q), MN1 overexpression in inv(1 6) patients, and epigenetic and posttranscriptional silencing of CEBPA. Genome-wide gene-expression and microRNA-expression profiling identifying subgroups of CBF-AML patients with distinct molecular signatures, different clinical outcomes, or both, have also been reported. Summary Progress has been made in delineating the genetic basis of CBF-AML that will likely result in improved prognostication and development of novel, risk-adapted therapeutic approaches.