A 70-year-old man with multiple myeloma has bone pain, serum M-protein of 4.2 g/dL, and lytic lesions on X-ray. The pathological fractures result from osteoclast activation; which cytokine produced by myeloma cells is most responsible for this osteoclast activation?

• A Macrophage inflammatory protein-1α (MIP-1α/CCL3) ✓
• B Interleukin-6 (IL-6)
• C RANK-L (receptor activator of NF-κB ligand)
• D Interleukin-1β (IL-1β)

Explanation

Myeloma cells secrete MIP-1α (CCL3), which is the primary osteoclast-activating factor in multiple myeloma; it acts through CCR1 and CCR5 on osteoclast precursors to stimulate osteoclastogenesis independently of RANK-L. While RANK-L, IL-1β, and IL-6 all contribute to osteolysis to varying degrees, the dominant osteoclast activating factor specifically driving lytic bone disease in myeloma is MIP-1α. IL-6 primarily acts as a plasma cell growth/survival factor in myeloma.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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