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CD47 promotes myeloma cell growth through JAK-STAT3/MYC signalling and is targetable by ruxolitinib

Omar Faruq1,2, Deepak Iyer1,2, Patrick Wang1,2

  • 1Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.

British Journal of Haematology
|August 15, 2026
PubMed

Insights

Cluster of differentiation 47 (CD47) drives multiple myeloma growth by activating the JAK/STAT3-MYC pathway. Inhibiting this axis with ruxolitinib shows therapeutic promise, reducing cancer cells while sparing normal ones.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Cluster of differentiation 47 (CD47) is overexpressed in multiple myeloma (MM), aiding immune evasion.
  • The intrinsic oncogenic role of CD47 in MM proliferation and survival is not well understood.

Purpose of the Study:

  • To investigate the intrinsic role of CD47 in multiple myeloma.
  • To elucidate the signaling pathways regulated by CD47 in MM.
  • To evaluate the therapeutic potential of targeting the CD47-JAK/STAT3-MYC axis.

Main Methods:

  • Assessed CD47's effect on myeloma cell proliferation, cell cycle, and colony formation.
  • Analyzed CD47's impact on Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) and MYC signaling.
  • Utilized transcriptomic analysis of patient data to correlate CD47, STAT3, and MYC expression.
  • Investigated the efficacy of ruxolitinib (a JAK1/2 inhibitor) alone and in combination with bortezomib.

Main Results:

  • CD47 overexpression enhanced myeloma cell growth, accelerated cell cycle progression, and promoted anchorage-independent growth.
  • CD47 signaling activates the JAK/STAT3-MYC axis, evidenced by increased STAT3 phosphorylation and MYC upregulation.
  • High CD47 expression in patients correlates with enriched JAK-STAT3 and MYC pathways.
  • Ruxolitinib treatment reduced myeloma cell viability, induced apoptosis, and suppressed STAT3/MYC signaling.
  • Ruxolitinib demonstrated synergistic effects with bortezomib in myeloma cells and patient samples, with minimal toxicity to normal cells.

Conclusions:

  • CD47 acts as an intrinsic oncogenic driver in multiple myeloma by activating the JAK/STAT3-MYC signaling pathway.
  • The CD47-STAT3-MYC axis represents a novel and promising therapeutic target for multiple myeloma.
  • Targeting this axis offers a potential strategy for effective and selective MM treatment.
Keywords:
CD47STAT3c‐MYCmultiple myeloma (MM)ruxolitinib (Rux)

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