EFFICIENT TRANSPLANTATION OF BCR-ABL-INDUCED CHRONIC MYELOGENOUS LEUKEMIA-LIKE SYNDROME IN MICE
EFFICIENT TRANSPLANTATION OF BCR-ABL-INDUCED CHRONIC MYELOGENOUS LEUKEMIA-LIKE SYNDROME IN MICE
复制标题
DOI：
10.1073/pnas.90.8.3755
复制
发表时间：
1993-04-15
影响因子：
11.1
通讯作者：
WITTE, ON
中科院分区：
文献类型：
--
作者：
GISHIZKY, ML;JOHNSONWHITE, J;WITTE, ON
用表达P210 BCR-ABL cain的骨髓重建的致死性辐射小鼠发生骨髓增殖综合征，类似于人类慢性粒细胞白血病（CML）的初始阶段。发展CML样综合征的小鼠可以根据粒细胞疾病出现的潜伏期-早期发作（20周）分为两组。只有来自表现出迟发性CML样综合征的小鼠的细胞在移植到亚致死剂量照射的同基因受体中时才能有效地传播疾病。移植了迟发性小鼠CML细胞的小鼠发生了一系列起源于多能干细胞的造血系统疾病。慢性粒细胞增生可以通过连续移植到第二和第三受体小鼠中繁殖。大多数移植小鼠死于急性骨髓性白血病以及B和T淋巴细胞白血病。这些数据支持晚发型小鼠CML起源于具有高复制能力的多能祖细胞的观点。不能从发展早发CML样综合征的小鼠移植疾病表明，这种疾病可能起源于具有有限复制能力的更分化的祖细胞，这些祖细胞经历了克隆扩增，但没有永生化。尽管早发性和迟发性CML样综合征都表现出粒细胞增生，但这些疾病代表了似乎起源于不同造血细胞类型的不同疾病。迟发性CML样疾病和转移到第二受体提供了一个有用的小鼠模型与人类CML的慢性和急性期的功能。
Lethally irradiated mice reconstituted with bone marrow expressing P210 BCR-ABL cain develop myeloproliferative syndromes that resemble the initial phase of human chronic myelogenous leukemia (CML). Mice that develop the CML-like syndrome can be segregated into two groups based on the latency with which the granulocytic disease appears-early onset (20 weeks). Only cells from mice exhibiting the late-onset CML-like syndrome can efficiently propagate the disease when transplanted into sublethally irradiated syngeneic recipients. Mice engrafted with late-onset murine CML cells develop a range of hematopoietic disorders that originate from multipotent stem cells. The chronic granulocytic hyperplasia can be propagated by serial transplantation into secondary and tertiary recipient mice. The majority of transplanted mice succumb to acute myeloid and B- and T-lymphoid leukemias. These data support the idea that late-onset murine CML originates from a multipotent progenitor cell with a high replicating capacity. The inability to transplant the disease from mice developing the early-onset CML-like syndrome suggests that this disorder may originate from more differentiated progenitor cells with limited replication capacity that have undergone clonal expansion but are not immortalized. Although both early- and late-onset CML-like syndromes exhibit granulocytic hyperplasia, these disorders represent distinct diseases that appear to originate from different hematopoietic cell types. The late-onset CML-like disease and transfer to secondary recipients provides a useful murine model with features of the chronic and acute phases of human CML.