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• W4386817423 abstract "Sezary syndrome (SS) is a rare, aggressive leukemic variant of cutaneous T-cell lymphoma (CTCL) that lacks adequate therapeutic options and representative small-animal models. Here, we demonstrate that IL-15 is a critical CTCL growth factor. Importantly, an immunodeficient knock-in mouse model genetically engineered to express human IL-15 uniquely supported the growth of SS patient samples relative to conventional immunodeficient mouse strains. SS patient-derived xenograft (PDX) models recapacitated key pathological features of the human disease, including skin infiltration and spread of leukemic cells to the periphery, and maintained the dependence on human IL-15 upon serial in vivo passaging. Detailed molecular characterization of the engrafted cells by single-cell transcriptomic analysis revealed congruent neoplastic gene expression signatures but distinct clonal engraftment patterns. Overall, we document an important dependence of Sezary cell survival and proliferation on IL-15 signaling and the utility of immunodeficient humanized IL-15 mice as hosts for SS - and potentially other T and NK cell-derived hematologic malignancies - PDX model generation. Furthermore, these studies advocate the thorough molecular understanding of the resultant PDX models to maximize their translational impact." @default.
• W4386817423 created "2023-09-19" @default.
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• W4386817423 date "2023-10-01" @default.
• W4386817423 modified "2023-10-15" @default.
• W4386817423 title "Microenvironment-dependent growth of Sezary cells in humanized IL-15 mice" @default.
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• W4386817423 doi "https://doi.org/10.1242/dmm.050190" @default.
• W4386817423 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37718909" @default.
• W4386817423 hasPublicationYear "2023" @default.
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