Advances in Molecular Genetics and Treatment of Core-binding Factor Acute Myeloid Leukemia

Overview

Journal Curr Opin Oncol

Specialty Oncology

Date 2008 Oct 9

PMID 18841055

Citations 31

Authors

Krzysztof Mrozek

Guido Marcucci

Peter Paschka

Clara D Bloomfield

Affiliations

Soon will be listed here.

Abstract

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(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.

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.

Citing Articles

White blood cell count levels are associated with inflammatory response and constitute independent outcome predictors in adult patients with acute myeloid leukemia aged <60 years.

Ozga M, Nicolet D, Mrozek K, Walker C, Blachly J, Kohlschmidt J Am J Hematol. 2024; 99(11):2236-2240.

PMID: 39283025 PMC: 11469947. DOI: 10.1002/ajh.27465.

Molecular dissection of a hyper-aggressive CBFB-MYH11/FLT3-ITD-positive acute myeloid leukemia.

Lo Iudice G, De Bellis E, Savi A, Guarnera L, Massacci A, De Nicola F J Transl Med. 2022; 20(1):311.

PMID: 35794567 PMC: 9258203. DOI: 10.1186/s12967-022-03486-5.

Gene Mutations, rs16754 Variant, and Overexpression as Prognostic Factors in Acute Myeloid Leukemia Patients.

Koczkodaj D, Zmorzynski S, Grygalewicz B, Pienkowska-Grela B, Styk W, Popek-Marciniec S J Clin Med. 2022; 11(7).

PMID: 35407481 PMC: 9000045. DOI: 10.3390/jcm11071873.

Secondary cytogenetic abnormalities in core-binding factor AML harboring inv(16) vs t(8;21).

Han S, Mrozek K, Voutsinas J, Wu Q, Morgan E, Vestergaard H Blood Adv. 2021; 5(10):2481-2489.

PMID: 34003250 PMC: 8152510. DOI: 10.1182/bloodadvances.2020003605.

Clinical heterogeneity under induction with different dosages of cytarabine in core binding factor acute myeloid leukaemia.

Wang B, Zhang J, Hua X, Li H, Wang Z, Yang B Sci Rep. 2020; 10(1):685.

PMID: 31959790 PMC: 6971028. DOI: 10.1038/s41598-020-57414-y.

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