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Semin Oncol. 2008 Aug;35(4):346-55. doi: 10.1053/j.seminoncol.2008.04.005.

Prognostic implications of gene mutations in acute myeloid leukemia with normal cytogenetics.

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  • 1Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.


In recent years, a number of somatically acquired mutational changes have been identified in patients with acute myeloid leukemia (AML). Most of these genetic alterations occur in AML exhibiting a normal karyotype, representing the largest cytogenetic subgroup (40%-50%) of AML. These molecular findings not only provide novel insights into the pathogenesis of AML but also are of clinical importance. In this review we will discuss the most relevant gene alterations, including NPM1 gene mutations, internal tandem duplications (ITD) or tyrosine kinase domain (TKD) mutations of the FLT3 gene, CEBPA gene mutations, and partial tandem duplications (PTD) of the MLL gene, as well as mutations in the NRAS and WT1 genes. In part, these gene mutations have emerged as important prognostic markers and they now allow us to dissect cytogenetically normal (CN)-AML in distinct prognostic subgroups. Furthermore, these mutant molecules represent potential targets for molecular therapies.

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