Junctional Adhesion Molecule-A (JAM-A) Associates With High-Risk Disease in Multiple Myeloma Patients and a Structure-Based Rationally-Designed Peptide Inhibitor Attenuates Tumorigenic Features In Vitro and In Vivo.
Junctional Adhesion Molecule-A (JAM-A) is getting attention in multiple myeloma research for good reason. Researchers in Dublin have zeroed in on JAM-A as a marker of high-risk disease. They didn’t stop there—they also built a peptide inhibitor that puts the brakes on tumor features in both cell lines and animal models.
Eur J Haematol
by McAuley N, McAvera R, Bong D et al.
“Junctional Adhesion Molecule-A (JAM-A) Associates With High-Risk Disease in Multiple Myeloma Patients and a Structure-Based Rationally-Designed Peptide Inhibitor Attenuates Tumorigenic Features In Vitro and In Vivo. McAuley N(1)(2), McAvera R(2), Bong D(1), Donnelly L(1), Cymer I(1)(2), Brennan M(3), Fay J(4), Hudson L(1), Quinn J(5), Glavey SV(2)(4)(5)(6), Hopkins AM(1)(6). Author information: (1)Department of Surgery, RCSI University of Medicine and Health Sciences, Dublin, Ireland. (2)Myeloma Research Group, RCSI University of Medicine and Health Sciences, Dublin, Ireland. (3)School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland. (4)Department of Pathology, RCSI University of Medicine and Health Sciences, Dublin, Ireland. (5)Department of Haematology, Beaumont Hospital, Dublin, Ireland. (6)Beaumont RCSI Cancer Centre, Dublin, Ireland. Multiple myeloma (MM) is an incurable malignancy of terminally-differentiated plasma cells that represents a major clinical challenge despite unprecedented therapeutic advances, particularly for patients with cytogenetically-defined high-risk MM (HR-MM). Updated in 2025, the evolving cytogenetic classification of HR-MM includes gains or amplifications in chromosome 1q. One gene of emerging interest on chromosome 1q is F11R, which codes for a protein called Junctional Adhesion Molecule-A (JAM-A). Upregulation of JAM-A has been linked with the development of several aggressive malignancies, most recently MM. In the current study, F11R gene expression was found to be significantly higher in gain/amp(1q) MM patients from the CoMMpass database, and to correlate with poorer overall survival in MM patients. Furthermore, elevated F11R expression was accompanied by an increased burden of circulating CD138+ cells, potentially an early hallmark of extramedullary disease (EMD). As JAM-A signalling putatively promotes tumorigenic behaviour through cis-dimerization-dependent adhesion signalling, structure-based rational design principles were utilised to design novel peptide inhibitors that selectively disrupt JAM-A cis-dimerization. In vitro testing of novel peptides across a panel of MM cell lines and primary CD138+ cells from MM patients demonstrated anti-proliferative and pro-senescence properties of the novel peptides. Moreover, candidate peptide P4 significantly inhibited the growth of CD138+ plasmacytoma-like tumours in an in vivo xenograft model involving implantation onto the chick chorioallantoic membrane. Collectively, these findings support the validity of JAM-A as an emerging druggable target and provide a strong rationale for further preclinical investigations of JAM-A inhibitors in MM. © 2026 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.”
Here’s what matters: High JAM-A (coded by F11R on chromosome 1q) shows up in patients with aggressive, high-risk multiple myeloma. These patients have more circulating CD138+ cells, which could be an early sign of the disease spreading outside the bone marrow. That’s a big deal, because managing extramedullary disease remains a real challenge.
Instead of just pointing fingers at JAM-A, the team used structural biology to design peptides that block JAM-A’s dimerization—basically, stopping the protein from signaling tumor cells to keep growing. They tested these peptides on multiple myeloma cells from both established lines and real patient samples.
Key takeaways:
Peptides targeting JAM-A slowed cell growth and pushed tumor cells toward senescence.
One standout, called P4, shrank tumors in a chick embryo model.
JAM-A is officially on the radar as a promising target for future peptide-based research in multiple myeloma.
Peptide research continues to unlock new ways to influence complex cell signaling—this JAM-A story is a strong example. The next step is more preclinical work, but the path looks promising for anyone developing or sourcing research peptides. Curious about other breakthroughs? Check the peptide research index for more updates on novel targets and compound design.
Keep an eye on JAM-A—there’s real momentum behind peptide innovation in this space.
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