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NPM1 mutations confer a favorable prognosis in older patients (≥60 years) with cytogenetically normal acute myeloid leukemia, particularly those aged ≥70 years, and are associated with gene and microRNA expression profiles similar to those seen in younger patients. Novelty: ClaimNovelty.CONFIRMATORY. Consensus alignment: ConsensusAlignment.NEUTRAL.

December 21, 2009Open Access

Favorable Prognostic Impact of NPM1 Mutations in Older Patients With Cytogenetically Normal De Novo Acute Myeloid Leukemia and Associated Gene- and MicroRNA-Expression Signatures: A Cancer and Leukemia Group B Study

Key Points

To examine the prognostic significance of NPM1 mutations and associated gene- and microRNA-expression signatures in older patients with de novo cytogenetically normal acute myeloid leukemia (CN-AML).
Analyzed 148 adults age ≥ 60 years with de novo CN-AML enrolled in Cancer and Leukemia Group B protocols 9720 and 10201.
Evaluated mutations in NPM1, FLT3, CEBPA, and WT1, along with gene- and microRNA-expression profiles at diagnosis.
Studied outcomes including complete remission, disease-free survival, and overall survival for patients stratified by NPM1 mutation status.
Patients with NPM1 mutations showed higher complete remission rates of 84% vs. 48% (P < .001).
Three-year overall survival rates were 35% for NPM1 mutation patients vs. 8% for wild-type (P < .001).
The favorable prognostic impact of NPM1 mutations was primarily significant in patients aged ≥ 70 years.

Abstract

PURPOSE: To analyze the prognostic significance of NPM1 mutations, and the associated gene- and microRNA-expression signatures in older patients with de novo, cytogenetically normal acute myeloid leukemia (CN-AML) treated with intensive chemotherapy. PATIENTS AND METHODS: One hundred forty-eight adults age >or= 60 years with de novo CN-AML, enrolled onto Cancer and Leukemia Group B protocols 9720 and 10201, were studied at diagnosis for NPM1, FLT3, CEBPA, and WT1 mutations, and gene- and microRNA-expression profiles. RESULTS: Patients with NPM1 mutations (56%) had higher complete remission (CR) rates (84% v 48%; P or= 70 years. Gene- and microRNA-expression profiles associated with NPM1 mutations were similar across older patient age groups and similar to those in younger (or= 70 years. The gene- and microRNA-expression profiles suggest that NPM1 mutations constitute a marker defining a biologically homogeneous entity in CN-AML that might be treated with specific and/or targeted therapies across age groups.

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