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


RESULTS
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(16) 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.


CONCLUSIONS
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.
Mrózek
Krzysztof
K
Division of Hematology and Oncology, Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210-1228, USA. krzysztof.mrozek@osumc.edu
Marcucci
Guido
G
Paschka
Peter
P
Bloomfield
Clara D
CD
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D003582:Cytogenetics; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000628:therapy*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis
D035683:MicroRNAs