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Vick, B. ; Jurinovic, V. ; Kuhbandner, K.* ; Lagally, L. ; Latzko, L.* ; Arnreich, C. ; Hänel, G.* ; Muth, A.* ; Schönung, M.* ; Kloos, A.* ; Rothenberg‐Thurley, M.* ; Dufour, A.M.* ; Schneider, S.E.* ; Holdt, L.M.* ; Mura, L. ; Klein, F. ; Frank, A. ; Mehra, D. ; Fröhlich, A. ; Bagnoli, J.* ; Andre, M.C.* ; Baldus, C.D.* ; Carroll, M.P.* ; Dierks, C.* ; Ebinger, M.* ; Götze, K.S.S.* ; Menéndez, P.R.* ; Récher, C.* ; Sahal, A.* ; Sarry, J.* ; Thiede, C.* ; Velasco-Hernández, T.* ; Wei, X.* ; Klusmann, J.* ; Enard, W.* ; Bergwelt‐Baildon, M.v.* ; Hiddemann, W.* ; Metzeler, K.H.* ; Greif, P.A.* ; Heuser, M.* ; Lipka, D.B.* ; Subklewe, M.S.* ; Vosberg, S.* ; Herold, T. ; Spiekermann, K.* ; Jeremias, I.

A platform of serially transplantable AML PDX models covering subgroups for which no cell lines exist.

Hemasphere 10:e70497 (2026)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Acute myeloid leukemia (AML) is a highly aggressive malignancy with poor prognosis, underlining the need for suitable model systemsto develop novel treatments. To complement the few existing AML cell lines and restricted primografts, we transplanted more than100 primary AML samples into immunocompromised mice and generated 23 exceptionally robust patient‐derived xenograft (*PDX)models of AML that allow virtually unlimited serial transplantation and efficient genetic engineering. These models represent in-dividuals of all age groups and several WHO subgroups. *PDX models substantially outperform AML cell lines in preserving leukemiabiology and include AML subgroups for which no cell lines exist, such as cytogenetically normal or IDH1/2‐mutant AML or si-multaneous NPM1 mutation and FLT3‐ITD. Their resilience to freeze‐thaw cycles supports broad dissemination across researchinstitutions through sharing via CancerModels.org. Using lentiviruses, we stably expressed luciferase for longitudinal, noninvasive, andsensitive real‐time monitoring of leukemia burden and therapeutic response in vivo. This approach enabled rigorously controlledpreclinical studies, including phase II‐like trials, which demonstrated highly variable treatment responses between different *PDXmodels, mimicking the heterogeneity in patient cohorts. Long‐term treatment, including repeated cytarabine exposure over 1 year,showed a yet undescribed decrease in leukemia's proliferation rate. These insights underscore the platform's distinctive capacity tostudy treatment dynamics over clinically relevant timeframes. Collectively, our unique resource represents a powerful, robust, andversatile platform with strong potential to accelerate translational AML research for the ultimate benefit of patients.
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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 2572-9241
e-ISSN 2572-9241
Journal Hemasphere
Quellenangaben Volume: 10, Issue: 10, Pages: , Article Number: e70497 Supplement: ,
Publisher Wiley
Reviewing status Peer reviewed
Institute(s) Research Unit Apoptosis in Hematopoetic Stem Cells (AHS)