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Variant Allele Frequency in MDS

Do gene mutations have prognostic value?

Publish date:: November 4, 2015

Variant allele frequency (VAF) should be incorporated in patient management and risk stratification in myelodysplastic syndromes (MDS), according to a study of TP53 and 20 additional genes from 219 patients with MDS or secondary acute myeloid leukemia. Researchers found:

• When parsed by VAF, TP53 VAF predicted for complex cytogenetics in 2 separate cohorts.

• Patients with MDS and and TP53 VAF > 40% had a median overall survival (OS) of 124 days vs an OS that was not reached in a cohort with VAF > 20%.

• TP53 VAF further stratified distinct prognostic groups independent of clinical prognostic scoring systems.

• In multivariate analysis, only TP53 VAF > 40% was an independent covariate.

• SRSF2 VAF predicted for monocytosis, RUNX1 VAF with thrombocytopenia, and SF3B1 with ringed sideoblasts.

Citation: Sallman DA, Komrokji R, Vaupel C, et al. Impact of TP53 mutation variant allele frequency on phenotype and outcomes in myelodysplastic syndromes. [Published online ahead of print October 30, 2015]. Leukemia. doi: 10.1038/leu.2015.304.

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