Prognostic value of PRDM16 expression in NPM1mut AML

Results from a retrospective analysis, evaluating the prognostic value of PRDM16 expression in 503 adults with newly diagnosed NPM1-mutated (NPM1^mut) acute myeloid leukemia (AML), were published in Annals of Hematology by Stasik et al. The association between PRDM16 expression and DNMT3A and FLT3-ITD co-mutational status, including double- and triple-mutant genotypes, was analyzed.

Key data: In the overall NPM1^mut cohort, PRDM16 expression was not associated with overall survival (OS; p = 0.2291). PRDM16 expression was analyzed across four levels (low; intermediate-I; intermediate-II; high), with similar rates of complete remission (CR) across groups (81.7–84.0%). High PRDM16 expression was associated with enrichment of DNMT3A and FLT3-ITD mutations and a corresponding higher proportion of ELN2022 intermediate-risk disease compared with low PRDM16 expression; however, it was not independently associated with clinical outcomes after adjustment for ELN2022 risk in the overall NPM1^mut AML cohort. In the double-mutated NPM1/FLT3-ITD subgroup (n = 200), low PRDM16 expression was associated with a longer median OS (65.3 vs 10.4 months; p = 0.0065) compared with intermediate/high PRDM16 expression, and remained an independent prognostic factor after adjustment (hazard ratio [HR], 0.467; 95% confidence interval [CI], 0.270–0.807; p = 0.006).

Key learning: Low PRDM16 expression was identified as a favorable-risk prognostic marker in patients with NPM1^mut/FLT3-ITD AML, supporting its potential to refine prognostic stratification beyond conventional genetics in this otherwise adverse-risk molecular subgroup.