Defective neutrophil clearance in JAK2V617F myeloproliferative neoplasms drives myelofibrosis via immune checkpoint CD24.

ABSTRACT:

Abstract

Myeloproliferative neoplasms (MPNs) are hematopoietic stem cell-driven malignancies marked by excessive myelopoiesis and high risk of myelofibrosis, which remains therapeutically challenging. Senescent neutrophils home daily to the bone marrow (BM) to be cleared by macrophages. This avoids their accumulation, which can increase the risk of chronic inflammation or oncogenesis. Neutrophils carrying the most common oncogenic MPN driver (JAK2V617F) are protected from apoptosis, which may prolong their life span and enhance their proinflammatory activity. In contrast, abnormal interactions of neutrophils with megakaryocytes ("emperipolesis") have been associated with BM fibrosis in disparate hematologic disorders, including MPN and gray platelet syndrome; however, the underlyin

SUBMITTER: Khatib-Massalha E 

PROVIDER: S-EPMC7618514 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature