Does disease ontogeny matter more than JAK2 mutation status in acute myeloid leukemia?

Does disease ontogeny matter more than JAK2 mutation status in acute myeloid leukemia?We read with great interest the study by Albliwi et al. 1 evaluating cytokine receptor and JAK/STAT pathway mutations in acute myeloid leukemia (AML) and their clinical significance.The authors are to be congratulated for assembling a large cohort and providing valuable insights into the heterogeneous biology of these uncommon genomic alterations.However, we believe one of the most important messages of the study extends beyond the prognostic implications of JAK2 mutations themselves.A particularly striking observation was the marked outcome disparity between patients with blast-phase myeloproliferative neoplasms (MPN-BP) and those with de novo AML harboring JAK2/ CALR/MPL mutations.Despite sharing similar driver mutations, patients with MPN-BP experienced substantially lower remission rates and inferior survival.Furthermore, JAK2 mutations were associated with adverse outcomes in univariable analyses but lost prognostic significance after adjustment for established high-risk variables.