Myelofibrosis osteoclasts are clonal and functionally impaired.

ABSTRACT: Bone marrow (BM) sclerosis is commonly found in patients with late-stage myelofibrosis (MF). Because osteoclasts (OCs) and osteoblasts play a key role in bone remodeling, and MF monocytes, the OC precursors, are derived from the neoplastic clone, we wondered whether decreased OC numbers or impairment in their osteolytic function affects the development of osteosclerosis. Analysis of BM biopsies from 50 MF patients showed increased numbers of multinucleated tartrate-resistant acid phosphatase (TRAP)/cathepsin K⁺ OCs expressing phosphorylated Janus kinase 2 (JAK2). Randomly microdissected TRAP⁺ OCs from 16 MF patients harbored JAK2 or calreticulin (CALR) mutations, confirming MF OCs are clonal. To study OC function, CD14⁺ monocytes from MF patie

SUBMITTER: Veletic I 

PROVIDER: S-EPMC6533604 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature