Enhanced engraftment of human myelofibrosis stem and progenitor cells in MISTRG mice
作者： Veronika Lysenko , Nicole Wildner-Verhey van Wijk , Kathrin Zimmermann , Marie-Christine Weller , Marco Bühler
DOI: 10.1182/BLOODADVANCES.2019001364
关键词:
摘要: The engraftment potential of myeloproliferative neoplasms in immunodeficient mice is low. We hypothesized that the physiological expression human cytokines (macrophage colony-stimulating factor, interleukin-3, granulocyte-macrophage and thrombopoietin) combined with signal regulatory protein α Rag2-/-Il2rγ-/- (MISTRG) might provide a supportive microenvironment for development maintenance hematopoietic stem progenitor cells (HSPC) from patients primary, post-polycythemia or post-essential thrombocythemia myelofibrosis (MF). show MISTRG mice, contrast to standard NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ supported all patient samples investigated independent MF disease stage risk category. Moreover, exhibited significantly higher levels bone marrow, peripheral blood, spleen secondary repopulation. Bone marrow fibrosis was limited 3 14 mice. Disease-driving mutations were identified xenografts, targeted sequencing revealed primary sample clonal composition 7 8 cases. Treatment engrafted current standard-of-care Janus kinase inhibitor ruxolitinib led reduction chimerism. In conclusion, established patient-derived xenograft model supports robust HSPCs maintains genetic complexity observed patients. suited further testing novel therapeutic agents expedite their transition into clinical trials.
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