ORIGINAL RESEARCH article
Front. Immunol.
Sec. B Cell Biology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1643615
RUNX1 Expression Dynamics in Plasma Cell Differentiation and Pathogenesis of Multiple Myeloma
Provisionally accepted
Ting Fang Tang1
YEE TENG CHAN1
Hui Jing Lim1Nur Adila Anuar1Chin Sum Cheong1
Chung Yeng Looi2Sen Mui Tan3
Won Fen Wong1*Gin Gin Gan1*- 1University of Malaya, Kuala Lumpur, Malaysia
- 2Taylor's University, Subang Jaya, Malaysia
- 3Hospital Ampang, Ampang Jaya, Malaysia
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Multiple myeloma (MM) is characterized by the malignant proliferation of plasma cells within the bone marrow. The transcriptional mechanisms governing plasma cell differentiation and MM pathogenesis are regulated by an intricate network of transcription factors, the role of RUNX1 in this process remains poorly defined. This study aimed to characterize plasma cell subsets in MM and evaluate the expression and functional role of RUNX1 during B cell differentiation. Bone marrow and peripheral blood samples were collected from 61 MM patients and 18 healthy donors. Flow cytometry was used to identify B cell and plasma cell subsets and measure RUNX1 expression across B cell maturation stages. Functional validation was conducted via siRNA-mediated RUNX1 knockdown in CD19⁺ B cells followed by in vitro plasma cell differentiation assays. Our data showed that MM patients exhibited significantly increased proportions of plasma cells in bone marrow compared to healthy controls. Intriguingly, RUNX1 expression was low in naive B cell subsets but increased progressively through plasmablast, pre-plasma, and plasma stages. Although RUNX1 expression did not significantly differ across MM stages or between newly diagnosed and relapsed/refractory cases, plasmablasts from MM patients showed higher RUNX1 levels than those from controls. Knockdown of RUNX1 in vitro using siRNA delayed B cell differentiation transiently. In summary, RUNX1 expression is dynamically upregulated during terminal B cell differentiation and is elevated in MM-derived plasmablasts. These findings provide new insights into a potential role for RUNX1 in the B cell differentiation axis and MM disease progression.
Keywords: Multiple Myeloma, Plasma Cells, Runx1, B cell differentiation, plasmablast
Received: 09 Jun 2025; Accepted: 14 Aug 2025.
Copyright: © 2025 Tang, CHAN, Lim, Anuar, Cheong, Looi, Tan, Wong and Gan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Won Fen Wong, University of Malaya, Kuala Lumpur, Malaysia
Gin Gin Gan, University of Malaya, Kuala Lumpur, Malaysia
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