Leukemic stem cell subtypes determine venetoclax resistance and therapeutic vulnerabilities in AML
monocytic AMLs, drive venetoclax resistance. LSC subtyping improves genetic risk stratification and provides subtype-specific therapies: venetoclax-resistant MEP-LSCs respond to BCL-xL inhibitors, whereas MoDe-LSCs are sensitive to MEK1/2 inhibition. Our findings reveal four distinct LSC types with unique vulnerabilities and propose biomarker-guided treatment strategies that complement genetic profiling to overcome venetoclax resistance.
Authors
- Elisa Donato (ORCID: https://orcid.org/0000-0003-3541-9170)
- Markus Sohn
- Maike Janssen (ORCID: https://orcid.org/0000-0001-9899-1022)
- Maria‐Eleni Lalioti (ORCID: https://orcid.org/0000-0003-3411-7832)
- Aino‐Maija Leppä (ORCID: https://orcid.org/0000-0003-0849-1759)
- Barbara Betz (ORCID: https://orcid.org/0000-0002-2767-5062)
- Simon Renders (ORCID: https://orcid.org/0000-0001-7883-2956)
- Karolin Stumpf (ORCID: https://orcid.org/0000-0002-8930-7265)
- Vera Thiel (ORCID: https://orcid.org/0000-0003-1245-0175)
- Nina Cabezas‐Wallscheid (ORCID: https://orcid.org/0000-0003-0870-0530)
- Alexander Waclawiczek (ORCID: https://orcid.org/0000-0002-8749-6736)
- Darja Karpova (ORCID: https://orcid.org/0000-0003-0695-1854)
- Mika Kontro (ORCID: https://orcid.org/0000-0001-6353-0664)
- Frank Y. Huang (ORCID: https://orcid.org/0000-0002-2163-9300)
- Rabia Shahswar (ORCID: https://orcid.org/0000-0001-6266-6316)
- Simon Raffel (ORCID: https://orcid.org/0000-0003-4671-1097)
- Andreas Trumpp (ORCID: https://orcid.org/0000-0002-6212-3466)
- Michael Hundemer (ORCID: https://orcid.org/0000-0002-5596-2405)
- Tim Sauer (ORCID: https://orcid.org/0000-0001-5412-324X)
- Ines Bergerweiss
- Sarah Richter (ORCID: https://orcid.org/0009-0008-8222-7976)
- Christoph Röllig
- Susanna Gabrowski
- Julia M. Unglaub
- Heikki Kuusanmäki
- Carsten Müller-Tidow
- Ann-Kathrin Eisfeld
- Halvard Bonig
- Bendix Hempel
- Michael Heuser
Institutions
- Goethe University Frankfurt (DE)
- University of Helsinki (FI)
- German Cancer Research Center (DE)
- Heidelberg University (DE)
- German Red Cross (DE)
- University Hospital Heidelberg (DE)
- Medizinische Hochschule Hannover (DE)
- National Center for Tumor Diseases (DE)
- Institute for Molecular Medicine Finland (FI)
- Heidelberg Institute for Stem Cell Technology and Experimental Medicine (DE)
- Klinik und Poliklinik für Psychotherapie und Psychosomatik (DE)
- Max Planck Institute of Immunobiology and Epigenetics (DE)
- Deutsches Konsortium für Translationale Krebsforschung (DE)
- The Ohio State University (US)
- Martin Luther University Halle-Wittenberg (DE)
Publication Details
- Journal
- Cell stem cell
- Published
- 2026-05-01
- DOI
- https://doi.org/10.1016/j.stem.2026.04.012
- Primary Topic
- Acute Myeloid Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- European Molecular Biology Organization
- Wilhelm Sander-Stiftung
- Deutsche Forschungsgemeinschaft
- José Carreras Leukämie-Stiftung
- Deutsche Krebshilfe
- Deutschen Konsortium für Translationale Krebsforschung
- HORIZON EUROPE Framework Programme
- European Research Council