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• W2290201733 abstract "Juvenile myelomonocytic leukemia is a clonal malignant disease affecting young children. Current cure rates, even with allogeneic hematopoietic stem cell transplantation, are no better than 50%-60%. Pre-clinical research on juvenile myelomonocytic leukemia is urgently needed for the identification of novel therapies but is hampered by the unavailability of culture systems. Here we report a xenotransplantation model that allows long-term in vivo propagation of primary juvenile myelomonocytic leukemia cells. Persistent engraftment of leukemic cells was achieved by intrahepatic injection of 1×10(6) cells into newborn Rag2(-/-)γc(-/-) mice or intravenous injection of 5×10(6) cells into 5-week old mice. Key characteristics of juvenile myelomonocytic leukemia were reproduced, including cachexia and clonal expansion of myelomonocytic progenitor cells that infiltrated bone marrow, spleen, liver and, notably, lung. Xenografted leukemia cells led to reduced survival of recipient mice. The stem cell character of juvenile myelomonocytic leukemia was confirmed by successful serial transplantation that resulted in leukemia cell propagation for more than one year. Independence of exogenous cytokines, low donor cell number and slowly progressing leukemia are advantages of the model, which will serve as an important tool to research the pathophysiology of juvenile myelomonocytic leukemia and test novel pharmaceutical strategies such as DNA methyltransferase inhibition." @default.
• W2290201733 created "2016-06-24" @default.
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• W2290201733 date "2016-02-17" @default.
• W2290201733 modified "2023-09-26" @default.
• W2290201733 title "Long-term serial xenotransplantation of juvenile myelomonocytic leukemia recapitulates human disease in Rag2-/- c-/- mice" @default.
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• W2290201733 doi "https://doi.org/10.3324/haematol.2015.138545" @default.
• W2290201733 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5004370" @default.
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