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ASH 2025 | Multimodal assessment of CMML with extramedullary involvement reveals RAS pathway activation
Sanam Loghavi, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, discusses the findings of a study in which a multimodal assessment of chronic myelomonocytic leukemia (CMML) cases with extramedullary involvement was conducted. Dr Loghavi highlights that extramedullary disease in CMML was associated with RAS pathway activation, epithelial-mesenchymal transition, and diverse phenotypes. This interview took place at the 67th ASH Annual Meeting and Exposition, held in Orlando, FL.
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Transcript
Yeah, so this is a very interesting and exciting abstract that we have with Guillermo Montalban-Bravo, my colleague in leukemia at MD Anderson. And really, you know, we had known for years that patients with chronic myelomonocytic leukemia, or CMML, actually have this extramedullary manifestation, some of them have this extramedullary manifestation where sometimes they’ll present with a rash or leukemic involvement in the skin...
Yeah, so this is a very interesting and exciting abstract that we have with Guillermo Montalban-Bravo, my colleague in leukemia at MD Anderson. And really, you know, we had known for years that patients with chronic myelomonocytic leukemia, or CMML, actually have this extramedullary manifestation, some of them have this extramedullary manifestation where sometimes they’ll present with a rash or leukemic involvement in the skin. First of all, you know, the diagnosis, the diagnostic classification of these lesions can be very tricky because, you know, oftentimes they don’t actually look like, don’t look like straightforward leukemia cutis. Sometimes you’ll see features of CMML involving the skin, and then other times it looks like mature histiocytic proliferations involving the skin. So the thing that we wanted to highlight was, you know, several things. One was the phenotypic variation of this manifestation and that really all of this is underlying CMML and driven by CMML, and so even if it doesn’t look quite malignant, it’s still malignant and, you know, shares clonality with the CMML.
The other things that we found very interesting during the course of this study was that when you have CMML involvement in the skin and in extramedullary diseases, there’s this epithelial-mesenchymal transition program that’s turned on. And then the, you know, the highlight of this study is really the fact that almost all of these cases with extramedullary manifestations or extramedullary involvement have RAS pathway alterations, including KRAS being the most common and significant one. So again, it seems like the extramedullary manifestation is largely driven by RAS. And to that point, there is another study by Audrey Lasry. She’s actually presenting this data today, later today in the AML session that actually shows the same thing in AML, where extramedullary manifestation of AML is largely driven by RAS mutations. And this is very, you know, it’s very important because at the time we have pan-RAS inhibitors and we can target the RAS pathway. So very important, both prognostically, diagnostically, and therapeutically.
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