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Curr Opin Hematol. 2005 Jan;12(1):68-75.

Molecular heterogeneity and prognostic biomarkers in adults with acute myeloid leukemia and normal cytogenetics.

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1
Division of Hematology and Oncology, Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA. marcucci-1@medctr.osu.edu

Abstract

PURPOSE OF REVIEW:

Patients with acute myeloid leukemia (AML) and normal karyotype constitute the single largest cytogenetic group of AML, estimated to account for 45% of adults with de novo AML. This article critically reviews the recent literature that addresses the molecular heterogeneity of this group of patients and how this relates to prognostic stratification and novel therapeutic approaches.

RECENT FINDINGS:

Four prognostic biomarkers-the internal tandem duplication and point mutations in the FLT3 gene, partial tandem duplication of the MLL gene, mutations of the CEBPA gene, and overexpression of the BAALC gene-have been found to predict outcome in patients with AML and normal cytogenetics. In addition, one study using gene expression profiling identified two subgroups of AML patients with a normal karyotype whose survival differs significantly. Because mutations in FLT3 result in an autophosphorylated, leukemogenesis-driving protein, molecular targeting therapy with a new class of tyrosine kinase inhibitors is being explored in early clinical trials.

SUMMARY:

Considerable progress has been made in molecular characterization of AML patients with normal cytogenetics. The challenge for the future is to incorporate these biologic discoveries into novel risk-adapted therapeutic strategies that will improve the currently disappointing cure rate (approximately 25-40%) of this group of patients.

PMID:
15604894
[Indexed for MEDLINE]
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