Schlenk RF et al. (2008) Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med 358: 1909–1918

Patients with cytogenetically normal acute myeloid leukemia (AML) represent around 40–50% of all AML cases and are categorized as an intermediate-risk group. This group of patients is heterogeneous, with mutations occurring in several genes involved in different processes related to leukemogenesis, which can affect prognosis. Schlenk and colleagues, therefore, investigated the prognostic and predictive value of mutations in the following genes in patients with cytogenetically normal AML: nucleophosmin (NPM1); fms-related tyrosine kinase 3 (FLT3); CCAAT/enhancer binding protein α (CEBPA); myeloid–lymphoid or mixed-lineage leukemia (MLL); and the neuroblastoma RAS viral oncogene homolog (NRAS).

A total of 872 patients with newly diagnosed AML (aged 16–60 years) who were enrolled in four separate German–Austrian Acute Myeloid Leukemia Study Group trials were assessed. In all four trials, allogeneic stem-cell transplantation was recommended in patients with a related donor matched for human leukocyte antigen. Mutant NPM1, without FLT3-internal tandem duplication (ITD), and mutant CEBPA were significantly associated with complete remission after induction chemotherapy and were associated with a significantly better relapse-free and overall survival. Only patients with the genotypes FLT3-ITD or wild-type NPM1/CEBPA without FLT3-ITD benefited from allogeneic stem-cell transplantation; stem cell transplantation did not confer a survival benefit on patients with more-favorable genotypes.

The authors recommend that newly diagnosed patients with AML should be screened for NPM1, FLT3, and CEBPA mutations, as the data from such analyses provide important prognostic information and may influence the choice of post-remission therapy.