Spatial imaging unlocks the potential of charting multiple myeloma and extramedullary disease
Abstract Extramedullary disease (EMD) in multiple myeloma (MM) represents a significant clinical challenge, with a limited understanding of the spatial architecture and its pathobiological impact. To address this unmet need, we examined 10 matched samples from bone marrow (BM) and cognate EMD sites....
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BMC
2025-04-01
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| Series: | Journal of Hematology & Oncology |
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| Online Access: | https://doi.org/10.1186/s13045-025-01699-x |
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| author | Vanessa Desantis Alessandro Andriano Tim Düking Olga Hartwig Giuseppe Ingravallo Marta Biondo Cirino Botta Roberto Ria Angelo Vacca Antonio Giovanni Solimando |
| author_facet | Vanessa Desantis Alessandro Andriano Tim Düking Olga Hartwig Giuseppe Ingravallo Marta Biondo Cirino Botta Roberto Ria Angelo Vacca Antonio Giovanni Solimando |
| author_sort | Vanessa Desantis |
| collection | DOAJ |
| description | Abstract Extramedullary disease (EMD) in multiple myeloma (MM) represents a significant clinical challenge, with a limited understanding of the spatial architecture and its pathobiological impact. To address this unmet need, we examined 10 matched samples from bone marrow (BM) and cognate EMD sites. This investigation provides critical insights into the distinct features of EMD, offering potential avenues for more effective diagnosis and targeted therapies. To this aim, we employed MACSima™ Imaging Cyclic Staining (MICS) to unveil distinct biomarker expression profiles as companion diagnostics for a personalized therapeutic approach for MM. We observed elevated BCL-2 levels in EMD plasma cells (p < 0.0001), indicating the potential of BCL-2 inhibitors to target anti-apoptotic pathways in select cases. The higher expression of EZH2 in EMD compared to BM (p < 0.0001) highlights its role in sustaining aggressive tumor phenotypes and supports the use of epigenetic-targeting agents in key situations. In contrast, CD3 + T-cell distance was significantly higher in EMD, reflecting impaired immune surveillance (p < 0.0001). Across the cohort, our analysis revealed significant differences between BM and EMD regarding the expression and spatial organization of key markers. CD38 expression was markedly reduced in EMD plasma cells (p < 0.0001). These findings underscore profound biological heterogeneity in MM and its BM emancipated disease phenotype, emphasizing dysfunctional apoptosis, immune evasion and resistance to CD38-targeting therapies in EMD, conceivably informing future validations. By integrating high-dimensional data, this study provides insights into potential druggable vulnerabilities for crafted interventions, particularly challenging in EMD cases. |
| format | Article |
| id | doaj-art-4d36ff181e2e4f0fb66a1b10be013046 |
| institution | DOAJ |
| issn | 1756-8722 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Hematology & Oncology |
| spelling | doaj-art-4d36ff181e2e4f0fb66a1b10be0130462025-08-20T03:15:14ZengBMCJournal of Hematology & Oncology1756-87222025-04-011811510.1186/s13045-025-01699-xSpatial imaging unlocks the potential of charting multiple myeloma and extramedullary diseaseVanessa Desantis0Alessandro Andriano1Tim Düking2Olga Hartwig3Giuseppe Ingravallo4Marta Biondo5Cirino Botta6Roberto Ria7Angelo Vacca8Antonio Giovanni Solimando9Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), Section of Pharmacology, University of Bari Aldo Moro Medical SchoolDepartment of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), Section of Pharmacology, University of Bari Aldo Moro Medical SchoolMiltenyi Biotec B.V. & Co. KGMiltenyi Biotec B.V. & Co. KGPathological Anatomy Unit, Department of Emergency and Organ Transplantation, University of Bari Aldo MoroDepartment of General Surgery and Medical-Surgical Specialties, University of CataniaDepartment of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of PalermoInternal Medicine Guido Baccelli, University of Bari Aldo Moro Medical SchoolInternal Medicine Guido Baccelli, University of Bari Aldo Moro Medical SchoolInternal Medicine Guido Baccelli, University of Bari Aldo Moro Medical SchoolAbstract Extramedullary disease (EMD) in multiple myeloma (MM) represents a significant clinical challenge, with a limited understanding of the spatial architecture and its pathobiological impact. To address this unmet need, we examined 10 matched samples from bone marrow (BM) and cognate EMD sites. This investigation provides critical insights into the distinct features of EMD, offering potential avenues for more effective diagnosis and targeted therapies. To this aim, we employed MACSima™ Imaging Cyclic Staining (MICS) to unveil distinct biomarker expression profiles as companion diagnostics for a personalized therapeutic approach for MM. We observed elevated BCL-2 levels in EMD plasma cells (p < 0.0001), indicating the potential of BCL-2 inhibitors to target anti-apoptotic pathways in select cases. The higher expression of EZH2 in EMD compared to BM (p < 0.0001) highlights its role in sustaining aggressive tumor phenotypes and supports the use of epigenetic-targeting agents in key situations. In contrast, CD3 + T-cell distance was significantly higher in EMD, reflecting impaired immune surveillance (p < 0.0001). Across the cohort, our analysis revealed significant differences between BM and EMD regarding the expression and spatial organization of key markers. CD38 expression was markedly reduced in EMD plasma cells (p < 0.0001). These findings underscore profound biological heterogeneity in MM and its BM emancipated disease phenotype, emphasizing dysfunctional apoptosis, immune evasion and resistance to CD38-targeting therapies in EMD, conceivably informing future validations. By integrating high-dimensional data, this study provides insights into potential druggable vulnerabilities for crafted interventions, particularly challenging in EMD cases.https://doi.org/10.1186/s13045-025-01699-xMultiple myelomaMACSima™ imaging systemMICS technologyExtramedullary disease |
| spellingShingle | Vanessa Desantis Alessandro Andriano Tim Düking Olga Hartwig Giuseppe Ingravallo Marta Biondo Cirino Botta Roberto Ria Angelo Vacca Antonio Giovanni Solimando Spatial imaging unlocks the potential of charting multiple myeloma and extramedullary disease Journal of Hematology & Oncology Multiple myeloma MACSima™ imaging system MICS technology Extramedullary disease |
| title | Spatial imaging unlocks the potential of charting multiple myeloma and extramedullary disease |
| title_full | Spatial imaging unlocks the potential of charting multiple myeloma and extramedullary disease |
| title_fullStr | Spatial imaging unlocks the potential of charting multiple myeloma and extramedullary disease |
| title_full_unstemmed | Spatial imaging unlocks the potential of charting multiple myeloma and extramedullary disease |
| title_short | Spatial imaging unlocks the potential of charting multiple myeloma and extramedullary disease |
| title_sort | spatial imaging unlocks the potential of charting multiple myeloma and extramedullary disease |
| topic | Multiple myeloma MACSima™ imaging system MICS technology Extramedullary disease |
| url | https://doi.org/10.1186/s13045-025-01699-x |
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