DNMT3A Mutations Do Not Impact Clinical Outcome in Acute Leukemia

ORLANDO ­– Bone marrow mutated DNA methyltransferase (DNMT3A^mut) transcript level did not impact clinical outcomes neither during therapy nor during follow-up in patients with acute myeloid leukemia (AML), a study presented at the American Society of Hematology (ASH) 57^th Annual Meeting has shown.¹

DNMT3A is one of the most commonly mutated genes in AML, with a hot spot mutation at codon R882 occurring in 80% of DNMT3A^mut cases. Previous research has shown that DNMT3A^mut predicts for poor relapse-free and overall survival and is associated with age-related clonal hematopoiesis.

“DNMT3A mutation is a ‘founder’ mutation in the early leukemogenic process,” Verena Gaidzik, MD, of the University Hospital of Ulm Department of Internal Medicine III in Ulm, Germany, said during her presentation.

Therefore, researchers sought to evaluate whether minimal residual disease monitoring in patients with DNMT3A^mut can be used to predict prognosis and stratify patients based on risk.

For the study, researchers monitored minimal residual disease for the most common DNMT3A^mut in a large cohort of 181 adult patients with AML who were participating in 1 of 3 AMLSG treatment trials. The median age of the cohort was 50 years. Monitoring was performed using a cDNA-based real-time quantitative-polymerase chain reaction-assay.

Results showed that most patients had persistent DNMT3A^mut transcript levels with only 8 of 90 patients and 4 of 88 patients achieving minimal residual disease negativity after double induction and end of therapy, respectively.

“We observed the greatest transcript level reduction after first induction with persistent DNMT3A^mut transcript levels in most patients during therapy, follow-up, and relapse, which supported the findings of persistent clonal hematopoiesis,” Dr Gaidzik concluded.

Dr Gaidzik noted that a serial investigation of DNMT3A^mut and its concurrent mutations is needed to gain further insights into the clonal architecture of AML.

Reference

1. Gaidzik VI, Weber D, Paschka P, et al. Monitoring of minimal residual disease (MRD) of DNMT3A mutations (DNMT3A^mut) in acute myeloid leukemia (AML): a study of the AML Study Group (AMLSG). Oral presentation at: 57^th American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.