BCR::ABL1-negative myeloproliferative neoplasms (MPNs), a family of slow-growing blood cancers, can evolve into secondary acute myeloid leukemia (sAML) or blast-phase (BP) MPN, which is a severe leukemia-like disease that is very difficult to treat. Researchers led by Ludwig Oxford’s Stefan Constantinescu explored the acquired genetic aberrations and patterns of clonal evolution that underlie transformation to BP-MPN using samples taken from 33 patients over six years at three hematology units in Romania. Aside from tracing the patterns of clonal evolution leading to BP-MPN, the researchers reported in an October Correspondence in the American Journal of Hematology that epigenetic mutations are detected in nearly 73% of cases. When copy-number variations that affect chromatin-modifying epigenetic enzymes and DNA methylation were additionally taken into account, nearly 85% of patients exhibited such genomic alterations, pointing to a major role for such mutations in MPN progression to BP-MPN. Anomalies in the EZH2 gene, which encodes a histone modifying enzyme, were especially common in people whose MPNs were driven by the common JAK2 V617F mutation or had none of the known driver mutations. Mutations in the TP53 gene were present in 33% of cases, with 75% of those also carrying epigenetic alterations. Stefan and his colleagues stress the importance of regular genetic screening of patients to evaluate clonal evolution as a means to predict disease transformation.
Dominance of mutations in epigenetic regulators and a diversity of signaling alterations in blast-phase BCR::ABL1-negative myeloproliferative neoplasms
American Journal of Hematology, 2024 October 19