Hematopoietic Stem and Progenitor Cell Fitness As a Novel Prognostic and Monitoring Biomarker for JAK2 V617F Myeloproliferative Neoplasms (MPNs)

Introduction: MPNs are chronic malignancies associated with significant morbidity and mortality due to cardiovascular events (CVE) and progression to more aggressive myeloid neoplasms (progression). CVE, progression, and survival are not feasible clinical trial endpoints due to the long follow-up required for analysis, leading to use of short-term measures. A reliable biomarker linking MPN biology with these important outcomes would facilitate development of new agents that can meaningfully reduce these risks and improve survival. Ultimately, MPNs result from hematopoietic stem cell (HSC) acquisition of highly recurrent driver mutations, most commonly JAK2 V617F. Here, we study MPN fitness - the competitive advantage of mutated hematopoietic stem and progenitor cells (HSPC) over their normal counterparts- as a prognostic and monitoring biomarker in MPNs, and compare it to whole blood (WB) mutation allele frequency (MAF).