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Blood, 15 January 2007, Vol. 109, No. 2, pp. 431-448.
Prepublished online as a Blood First Edition Paper on September 7, 2006; DOI 10.1182/blood-2006-06-001149.
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Submitted June 21, 2006
Accepted August 20, 2006
Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: are we ready for a prognostically prioritized molecular classification?
Krzysztof Mrozek*, Guido Marcucci, Peter Paschka, Susan P. Whitman, and Clara D. Bloomfield
Comprehensive Cancer Center, The Ohio State University, Columbus, OH
* Corresponding author; email: krzysztof.mrozek{at}osumc.edu.
Recent molecular analyses of leukemic blasts from pretreatment marrow or blood of patients with acute myeloid leukemia (AML) and a normal karyotype, the largest cytogenetic subset (i.e., 40-49%) of AML, has revealed a striking heterogeneity with regard to the presence of acquired gene mutations and changes in gene expression. Multiple submicroscopic genetic alterations with prognostic significance have been discovered, including internal tandem duplication of the FLT3 gene, mutations in the NPM1 gene, partial tandem duplication of the MLL gene, high expression of the BAALC gene, and mutations in the CEBPA gene. Application of gene-expression profiling has also identified a gene-expression signature that appears to separate cytogenetically normal AML patients into prognostic subgroups, although gene-expression signature-based classifiers predicting outcome for individual patients with greater accuracy are needed. These and similar future findings are likely to have a major impact on the clinical management of cytogenetically normal AML, not only in prognostication but also in selection of appropriate treatment, since many of the identified genetic alterations already constitute or will potentially become targets for specific therapeutic intervention. In this report, we review prognostic genetic findings in karyotypically normal AML and discuss their clinical implications.
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