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Differentiation of Functional Osteoclasts from Human Peripheral Blood CD14+ Monocytes
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Myelofibrosis osteoclasts are clonal and functionally impaired.

Ivo Veletic1, Taghi Manshouri1, Asha S Multani2

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Myelofibrosis osteoclasts, though increased, show impaired function. This reduced osteolytic activity contributes to bone sclerosis in myelofibrosis patients.

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Area of Science:

  • Hematology
  • Oncology
  • Bone Biology

Background:

  • Bone marrow sclerosis is common in advanced myelofibrosis (MF).
  • Osteoclasts (OCs) and osteoblasts are crucial for bone remodeling.
  • MF monocytes, OC precursors, originate from the neoplastic clone.

Purpose of the Study:

  • To investigate if impaired osteoclast function contributes to osteosclerosis in myelofibrosis.
  • To analyze the characteristics and function of OCs derived from MF patients.

Main Methods:

  • Analysis of bone marrow biopsies from 50 MF patients.
  • Culture and differentiation of CD14+ monocytes from MF patients and healthy individuals into OCs.
  • Assessment of OC morphology, number, nuclearity, and mineral resorption capacity.

Main Results:

  • MF patients exhibited increased numbers of multinucleated TRAP+/cathepsin K+ OCs expressing p-JAK2.
  • Clonal MF OCs harbored JAK2 or CALR mutations.
  • MF-derived OCs showed reduced size, fewer protrusions, decreased fusion events, and significantly impaired osteolytic function.

Conclusions:

  • Increased numbers of myelofibrosis-derived osteoclasts are present.
  • These osteoclasts possess impaired osteolytic function.
  • This functional deficit contributes to the development of osteosclerosis in myelofibrosis.