ADAM10: A New Precision Target for Acute Leukemia Therapy
New hope for acute leukemia patients: Helmholtz Munich researchers, led by Prof. Irmela Jeremias, have identified a promising therapeutic target, ADAM10, which could improve treatment strategies for relapsed leukemia. Their study, recently published in Molecular Cancer, highlights the potential of targeting leukemia stem cells to enhance treatment outcomes and pave the way for personalized cancer therapy.
Acute leukemias, devastating blood cancers, present a significant challenge due to their highly heterogenous nature in clinical presentation, genomic profile, and response to treatment. For patients suffering from relapsed disease, the prognosis remains particularly poor. These relapses typically originate from leukemia stem cells which hide in the protective bone marrow niche and depend on interactions with their surrounding microenvironment. The Helmholtz Munich Research Unit “Apoptosis in Hematopoietic Stem Cells” (AHS), led by Prof. Irmela Jeremias, is dedicated to identifying effective therapeutic targets to develop new personalized treatment strategies against these resilient leukemia stem cells.
In their recent study, the researchers unveiled a novel therapeutic approach by targeting surface molecules vital for the survival of leukemia stem cells. To faithfully mimic the situation in the patients, the team used clinically relevant genetically engineered patient-derived xenograft (PDX) models of acute leukemia, where the leukemia cells from patients grow in mice. By employing CRISPR/Cas9 for genetic knock-out screens, the team identified ADAM10 as a crucial surface molecule with an essential, yet previously unknown, function in acute leukemia. Their pre-clinical studies demonstrated that inhibiting ADAM10 – either molecularly or pharmacologically – significantly reduced the leukemia burden and the number of cancer stem cells in these models, while also enhancing the leukemia’s response to conventional chemotherapy.
“Our data suggest that ADAM10 might be a promising therapeutic target in acute leukemia. Additionally, the cutting-edge molecular in vivo approaches employed in my laboratory are paving the way for identifying further clinically relevant targets for personalized medicine and precision oncology”, concludes Prof. Jeremias.
Original publication
Bahrami et al. (2024) Combined proteomics and CRISPR‒Cas9 screens in PDX identify ADAM10 as essential for leukemia in vivo. Mol Cancer. DOI: 10.1186/s12943-023-01803-0
About the scientist
Prof. Irmela Jeremias, Head of the “Research Unit Apoptosis in Hematopoietic Stem Cells” at Helmholtz Munich
Funding information
Open Access funding enabled and organized by Projekt DEAL. The work was supported by the European Research Council Consolidator Grant 681524; a Mildred Scheel Professorship by German Cancer Aid; German Research Foundation (DFG) Collaborative Research Center 1243 (project A05); Deutsche José Carreras Leukämie-Stiftung (DJCLS 15 R/2021); German Cancer Corsortium (DKTK) Joint Funding RiskY-AML; Bettina Bräu Stiftung and Dr. Helmut Legerlotz Stiftung.
