Variant allele frequencies do not correlate well with myeloblast counts in a clinically validated gene sequencing panel for routine acute myeloid leukemia workup

Next generation sequencing (NGS) has introduced new types of data, such as variant allele frequencies (VAFs), into the workup of acute myeloid leukemias (AML). There is interest in using NGS to prognosticate disease behavior and monitor residual disease, but the attribution of sequencing data entirely to the leukemic clone may be confounded by VAF contribution from background non-leukemic populations and undetected copy number aberrations. Sixty-eight patients with AML were evaluated by a clinically validated gene sequencing panel at our institution from 2015 to 2018. No correlation was found with a direct comparison of blast counts and VAFs in both primary- and secondary-AML (R2 = 0.0584 and 0.0235, respectively). Only moderate correlations were attained when evaluating against mutant NPM1 allele fraction alone (R2 = 0.5303) or when variants with allelic frequencies >55% of the blast burden were excluded (R2 = 0.4608). VAFs from regular clinical-use gene sequencing panels show poor unrestricted correlation with leukemic blast proportions in AML.