Neutrophils in BCR::ABL1 negative MPN: Contributors or bystanders of fibrosis?

Abstract

BCR::ABL1 negative myeloproliferative neoplasms (MPNs) are a heterogenous group of disorders characterized by clonal proliferation of hematopoietic stem and progenitor cells (HSPCs) within the bone marrow. Although the identification of somatic key driver mutations significantly increased both understanding and diagnostic accuracy of MPNs, many questions about the exact pathophysiology remain unanswered. Increased neutrophil count at diagnosis is a well-recognized predictor of worse disease evolution and survival, nonetheless the exact role of neutrophilic granulocytes within MPN pathophysiology is almost unexplored. As the majority of these cells are residing within the bone marrow, they represent a non-negligible entity within the bone marrow niche and its homeostasis. This review describes how neutrophils might contribute to the development of the inflammatory bone marrow niche, and hereby also fibrosis, associated with MPNs. The versatile functions and effects in different contexts emphasize the necessity for future research oriented to bone marrow in addition to peripheral blood.