人T细胞急性淋巴细胞白血病小鼠动物模型的建立

目的:通过建立一理想的动物模型来模拟T细胞急性淋巴细胞白血病的发病状态,为探索急性淋巴细胞白血病全新的治疗方法提供平台。方法:采用抗鼠-CD122抗体注射NOD/SCID小鼠进行预处理,通过尾静脉注射9例不同病例的白血病细胞,以及1株T-ALL细胞系。通过检测小鼠体内白血病细胞及脏器白血病细胞浸润情况,观察白血病细胞植入。将白血病细胞进行二次移植,观察移植稳定性。对白血病动物模型进行药物处理,观察小鼠生存期,模拟人体治疗反应。结果:有4例病例的细胞及T-ALL细胞株成功植入。流式细胞检测显示受体小鼠体内较多比例人CD45+细胞表达,免疫组化显示CD45+细胞浸润小鼠不同脏器,系列移植也获得成功。体内药物处理显示地塞米松能延长小鼠的生存期,与临床观察相一致。结论:成功建立经抗鼠CD122单抗预处理的人T细胞急性淋巴细胞白血病NOD/SCID小鼠模型,具有原发疾病的所有主要特征。

Estabilishment of Mice Animal Model of T Cell AcuteLymphoblasitc Leukemia

Objective:To develop the animal models for understanding the pathophysiology of T cell acute lymphoblasticleukemia (T-ALL) and identifying novel therapeutic approaches.Methods:we inoculated the anti-mouse CD122 monoclonal antibodyconditioned NOD/SCID mice with the leukemia cells from 9 T-ALL patients and one cell line via the tail vein. Specimens obtained fromthese mice models were analyzed to confirm the engraftment of the leukemia cells. Serial transplanted leukemia cells from the secondarypassage of model to NOD/SCID mice for in vivo drug treatment were to mimick human responses.Results:Four of the 9 patients and thecell line were successfully engrafted. The high percentage of human CD45+ cells was detected in recipient mice by flow cytometry.Immunohistochemistry showed infiltration of human CD45+ cells in different organs. Serial transplantation was also achieved. In vivodrug treatment showed that dexamethasone could extend survival of rats, which was consistent with clinical observation.Conclusion:These results demonstrated that we successfully established 5 xenotransplantation model of T-ALL in anti-mCD122 mAb conditionedNOD/SCID mice, which recapitulated the characteristics of original disease.