DNMT3A Mutations Should be Considered in the Risk Stratification for Pediatric and Adolescent and Young Adult Patients with Acute Myeloid Leukemia

Background: Acute myeloid leukemia (AML) is rare but accounts for 20% of leukemia in the pediatric, adolescent and young adult (AYA) population. Five-year survival ranges widely from 22-90% based on subtype and cytogenetic abnormalities. The risk stratification of AML continues to evolve with increased recognition of inferior prognostic factors in the adult population; however, there has been a lack of similar progress in pediatrics. The DNA methyltransferase 3A (DNMT3A) mutation, most frequently at arginine 882 (DNMT3A mut) is observed in 14-34% of adult AML patients and is associated with inferior outcomes. This mutation shows evidence of anthracycline resistance, which may contribute to its poor prognosis as standard induction therapy for AML consists of a backbone of anthracyclines and purine analogs. Overall survival (OS) and disease-free survival (DFS) are improved in adult patients with DNMT3A mutation who receive consolidative allogeneic hematopoietic stem cell transplant (allo-HSCT). DNMT3A mutation has also been reported in the pediatric and AYA AML in 0-1.5% of cases with unclear prognostic implications. In case its presence in this patient population confers inferior outcomes similar to those seen in adults, these patients may also benefit from allo-HSCT