移植性慢性髓系白血病裸鼠模型的初步建立  

Preliminary Establishment of Transplanted Human Chronic Myeloid Leukemia Model in Nude Mice

作　　者：李先敏[1] 丁昕[2] 章龙珍[2] 岑建农[1] 陈子兴[1] 

机构地区：[1]苏州大学附属第一医院,江苏省血液研究所,江苏苏州215006 [2]徐州医学院附属医院放疗科,江苏徐州221002

出　　处：《中国实验血液学杂志》2011年第6期1378-1382,共5页Journal of Experimental Hematology

摘　　要：慢性髓系白血病(chronic myeloid leukemia,CML)是一种起源于造血干细胞的恶性克隆性疾病,CML干细胞被认为是导致疾病发生、发展并最终急变的根源,目前尚缺乏稳定的动物模型证明CML干细胞的存在。本研究旨在通过建立CML裸鼠模型,探讨人CML细胞在BABL/c裸小鼠体内的生物学行为,并使CML干细胞在裸鼠体内富集成为可能。对4至6周龄的BALB/c裸鼠进行切脾(splenectomy,S),环磷酰胺腹腔注射(cytoxan intrap-eritoneal injection,C)及全身亚致死剂量照射(sublethal irradiation,I)等预处理(SCI)后,经尾静脉接种(5-8)×107个人CML慢性期患者单个核细胞。对4至6周龄的BALB/c裸鼠进行全身致死剂量照射(lethal irradiation)后,经尾静脉接种5×106同源裸鼠骨髓细胞和(5-8)×107个人CML慢性期患者单个核细胞。应用RT-PCR、塑胶包埋病理切片以及流式细胞术等检测裸鼠各脏器及骨髓中人CML细胞浸润情况,并比较两种建模方法的优劣。结果表明,CML细胞能浸润至经SCI预处理的裸鼠骨髓体内,但目前成功率还很低,仅为通过BABL/c裸鼠建立人CML动物模型的一个开端。而经致死剂量预处理裸鼠,CML细胞未能浸润至骨髓。结论:人CML慢性期白血病细胞能在经SCI预处理的裸鼠体内形成白血病,为建立CML动物模型寻找到新的方向。Chronic myeloid leukemia（CML） is a malignant clonal disease derived from hematopoietic stem cells.CML stem cells were thought to be the root which could lead disease development and ultimately rapid change.However,a stable animal model for studying the characteristics of CML stem cells is currently lacking.This study was aimed to establish a transplanted human CML nude-mice model to further explore the biological behavior of CML stem cells in vivo,and to enrich CML stem cells in nude mice by series transplantation.The 4-6 weeks old BALB /c nude mice pretreated by splenectomy（S）,cytoxan intraperitoneal injection（C） and sublethal irradiation（I） were transplanted intravenously with（5-7）×10^7 of bone marrow mononuclear cells from CML patients in chronic phase.Alternatively,4-6 weeks old BALB /c nude mice pretreated by lethal irradiation were transplanted intravenously with 5×10^6 homologous bone marrow cells of BALB /c nude mice together with（5-7）×10^7 of bone marrow mononuclear cells from CML patients in chronic phase simultaneously.The leukemic cells engrafted and infiltrated in organs and bone marrow of the mice were tracked by reverse transcription-polymerase chain reaction（RT-PCR）,plastic-embedded biopsy and flow cytometry.The results of these two methods were compared.The results showed that human CML cells engrafted and infiltrating into the bone marrow of two nude mice pretreated with SCI could be detected.In spite of the low successful rate,results suggested the feasibility of this method by using BALB /c nude mice as a human CML animal model.In contrast,in nude mice pretreated by the lethal dose irradiation,CML cells in the bone marrow could not be found.It is concluded that human bone marrow CML cells can results in leukemia in nude mice pretreated by SCI.Thus this study provides a new strategy for establishment of CML animal models which deserves further elaboration.

关 键 词：慢性髓系白血病 慢性髓系白血病干细胞 动物模型 

分 类 号：R733.72[医药卫生—肿瘤] R-332[医药卫生—临床医学]