Should Patients with AML Undergo Routine Screening for Germline Variants?

By Ariel Jones - Last Updated: October 25, 2021

A study in Blood has found that nearly 14% of adult patients with acute myeloid leukemia (AML) have pathogenic or likely pathogenic germline variants that predispose them to developing myeloid malignancies. These findings support the need for routine screening of patients with AML for pathogenic germline variants, according to the study authors.

Researchers collected 391 tumor samples from patients with AML and matched skin biopsies. They also assessed patient electronic medical records to obtain data on clinical, prognostic, pathologic, cytogenetic, and molecular genetics.

To interpret the genetic screening results, investigators used the 2015 American College of Medical Genetics and Genomics (ACMG) guidelines for variant interpretation. They curated up to 1,547 unique variants from 228 genes. Pathogenic or likely pathogenic germline variants were identified in 13.6% of patients with AML (n=53), in a total of 34 genes. The most frequently mutated genes were identified in CHEK2 (n=8) and DDX41 (n=7).

Notably, 44% of the identified pathogenic germline variants were found in genes deemed “clinically actionable” by current guidelines. New candidate genes with pathogenic germline variants included DNAH5, DNAH9, DNMT3A, and SUZ12.