CO62 | CD9 defines the disease-propagating hematopoietic stem cell population in myelofibrosis

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic disorders, among which myelofibrosis (MF) represents the most severe form. MF is marked by progressive bone marrow fibrosis, worsening cytopenia, and a median overall survival of approximately five years. The disease originates from the expansion of a single hematopoietic stem and progenitor cell (HSPC) that has acquired somatic driver mutations in JAK2, CALR, or MPL, followed by additional cooperating mutations that promote clonal dominance over wild-type HSPCs. Although current therapies, including JAK inhibitors, provide symptomatic benefit, they fail to eradicate the malignant HSPC pool or induce molecular remission. Therefore, identifying and characterizing the stem cell population that sustains the MF clone is essential for developing curative strategies.