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IMS 2026 | Multi-omics reveals a molecular signature in TP53-mutated myeloma: insights & clinical implications

Wee Joo Chng, MB ChB, MRCP, MRCPath, PhD, National University of Singapore, Singapore, Singapore, discusses the significance of a molecular signature exclusive to myeloma cells with differential TP53 genetic perturbations, which can provide a window into understanding the biology of TP53-mutated multiple myeloma. Dr Chng highlights that this signature can help refine the identification and risk stratification of TP53-altered myeloma, and the goal is to translate these findings into simpler assays for use in community settings. This interview took place at the 23rd International Myeloma Society (IMS) Annual Meeting in Glasgow, UK.

These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.

Transcript

So as we know, TP53 mutation or inactivation represents one of the highest risk, poor outcome groups of patients there is in myeloma, even with all the advancements that I’ve just mentioned. These patients still do very badly. We know that they have TP53 inactivation. But what is unknown is what is the effect of this TP53 inactivation, right? TP53 mutation or inactivation is a marker, but what actually goes on in the cell when you have TP53 inactivated, particularly in the myeloma cells, is currently not very clear...

So as we know, TP53 mutation or inactivation represents one of the highest risk, poor outcome groups of patients there is in myeloma, even with all the advancements that I’ve just mentioned. These patients still do very badly. We know that they have TP53 inactivation. But what is unknown is what is the effect of this TP53 inactivation, right? TP53 mutation or inactivation is a marker, but what actually goes on in the cell when you have TP53 inactivated, particularly in the myeloma cells, is currently not very clear. And without knowing what it actually perturbs, we cannot think of better ways to actually treat these types of myeloma, right? Clearly, all the existing treatments don’t work very, very well. And so we need to understand what’s going on. And that’s the motivation behind our studies, which is to use different omics approaches comprehensively to study what goes wrong in a cell that has TP53 mutation. And what we found is a signature that will start to give us a window into understanding what is the biology that makes these myelomas so difficult to treat. That’s one important aspect. The other important aspect is clearly not many places will have access to multi-omics assays, right? But understanding this signature and identifying a signature, we’re hoping to also translate that into a simpler assay where we can then develop a simpler assay to identify what are the abnormalities rather than having to do multi-omics tests for all our patients. I think the biggest impact is on understanding the biology and maybe developing some better treatments for this group of patients. In terms of the biomarker, if the signature is a reflection of TP53 mutation, then I think the mutation detection alone is adequate, because that’s a relatively easier thing to do than to detect a complex signature. But I think the signature allows us to understand the biology which is more important for developing better treatments for this group of patients. So as I explained, I think the main effect is finding better, newer treatments. So once those treatments are tested and approved, then they can be easily applied in a community setting because I think in a community, unless you’re talking about very complex CAR-T treatment, if it’s a drug or something that inhibits a signaling pathway, they should be able to deliver that in a community setting.

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