Identifying acute myeloid leukemia gene mutations may indicate risk, best treatment

"Previous studies have found that AML is a highly heterogenic disorder," said study co-author Hugo F. Fernandez, a senior member at Moffitt and associate chief of Moffitt's Blood and Marrow Transplantation Division. "Moreover, recent studies have revealed that a number of genetic mutations in AML patients might have prognostic value. The question of the presence of these gene mutations altering outcomes based on current therapy had not been answered to date."

Their paper cites a clinical trial carried out by the Eastern Cooperative Oncology Group (ECOG) in which dose-intensified chemotherapy improved outcomes in two age sets of AML patients. Based on these findings, the research team hypothesized that carrying out mutational analysis of all known molecular alterations occurring in more than 5 percent of patients with AML might allow for the identification of distinct, molecularly defined subgroups of patients who might benefit from dose-intensified chemotherapy.

The laboratory research team subsequently performed a mutational analysis on diagnostic samples from 398 patients enrolled in the ECOG clinical trial they cited and used patients' frozen sample cells for extraction and profiling. The researchers validated the results of this latter group of 104 patients.

"We found that intensification of the dose of anthracycline significantly improved outcomes and overall survival in patients with mutations in DNMT3A, NPM1 or MLL translocations," said Fernandez. "This finding suggests that mutational profiling could be used to determine which AML patients will benefit from dose-intensive induction therapy."

"Most importantly," said Fernandez, "this study demonstrates how integrated mutational profiling of samples from a clinical trial cohort can advance understanding of the biologic characteristics of AML."

Journal reference: New England Journal of Medicine

Provided by H. Lee Moffitt Cancer Center & Research Institute