DNMT3A Mutations Do Not Impact Clinical Outcome in Acute Leukemia

Share this content:
Bone marrow mutated DNA methyltransferase (DNMT3Amut) transcript level did not impact clinical outcomes in acute myeloid leukemia.
Bone marrow mutated DNA methyltransferase (DNMT3Amut) transcript level did not impact clinical outcomes in acute myeloid leukemia.

ORLANDO ­– Bone marrow mutated DNA methyltransferase (DNMT3Amut) 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) 57th 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 DNMT3Amut cases. Previous research has shown that DNMT3Amut 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 DNMT3Amut can be used to predict prognosis and stratify patients based on risk.

For the study, researchers monitored minimal residual disease for the most common DNMT3Amut 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 DNMT3Amut 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.

RELATED: Individualized Prognostic Framework Predicts Risk in Acute Leukemia

“We observed the greatest transcript level reduction after first induction with persistent DNMT3Amut 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 DNMT3Amut 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 (DNMT3Amut) in acute myeloid leukemia (AML): a study of the AML Study Group (AMLSG). Oral presentation at: 57th American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.

Related Resources

You must be a registered member of Cancer Therapy Advisor to post a comment.

Sign Up for Free e-newsletters

Regimen and Drug Listings

GET FULL LISTINGS OF TREATMENT Regimens and Drug INFORMATION

Bone Cancer Regimens Drugs
Brain Cancer Regimens Drugs
Breast Cancer Regimens Drugs
Endocrine Cancer Regimens Drugs
Gastrointestinal Cancer Regimens Drugs
Gynecologic Cancer Regimens Drugs
Head and Neck Cancer Regimens Drugs
Hematologic Cancer Regimens Drugs
Lung Cancer Regimens Drugs
Other Cancers Regimens
Prostate Cancer Regimens Drugs
Rare Cancers Regimens
Renal Cell Carcinoma Regimens Drugs
Skin Cancer Regimens Drugs
Urologic Cancers Regimens Drugs