Peripheral Blood as a Method of Variant Detection in MDS

Peripheral blood (PB) may be used as a reliable method of variant detection in patients with myelodysplastic syndromes (MDS) and related conditions, according to results from the National MDS Natural History Study.

In this observational, longitudinal, cohort study, Amy DeZern, MD, MHS, of Johns Hopkins University, and colleagues compared somatic mutations and variant allele frequencies (VAFs) in paired PB and bone marrow (BM) samples to assess the efficacy of PB results as a tool for MDS diagnosis and monitoring.

Of the 36 cytopenic patients sampled, 10 had MDS, two had MDS/myeloproliferative neoplasms, one had acute myeloid leukemia, and 23 had clonal cytopenia of unknown significance. The study included only patients with a minimum of one variant detected in their BM, and five patients had circulating PB blasts.

The researchers identified 191 mutations, most commonly TET2 (27%), SRSF2 (13%), DNMT3A (9%), SF3B1 (8%), and ASXL1 (8%). According to a correlation analysis, shared mutations between paired PB and BM samples showed a linear relationship between VAFs detected in PB and BM.

BM mutations with higher VAFs were more likely to be detected, according to the researchers. Two mutations (ETNK1 and CBL) were detected in PB but not in BM.

Using linear regression, Dr. DeZern and colleagues assessed the relationship between percent of detected mutations and minimum VAF detected. The higher the minimum VAF, the lower the percentage of missed mutations.

The researchers concluded that if PB is positive, this method of variant detection may be used to diagnose and monitor MDS. However, if PB is negative, or if VAF is less than 0.10, then BM genomics are still necessary to exclude detectable clonal mutations.

Reference

DeZern A, Goll J, Jensen T, et al. Correlation between peripheral blood and bone marrow somatic mutations among patients with suspected or established myelodysplastic syndromes from the National MDS Study. Abstract #1860. Presented at the 65th ASH Annual Meeting & Exposition; December 9-12, 2023; San Diego, California.