Van Etten R A
The Center for Blood Research and Department of Genetics, Harvard Medical School, Boston MA 02115, USA.
Curr Oncol Rep. 2001 May;3(3):228-37. doi: 10.1007/s11912-001-0055-y.
Models of chronic myeloid leukemia (CML) have proven invaluable for furthering our understanding of the molecular pathophysiology of this disease. Xenotransplantation of primary human CML cells into immunodeficient mice allows investigation into the nature of the most primitive repopulating cells in this leukemia, but the system is limited by variability and difficulty with experimental manipulation. Accordingly, a large effort has been invested in developing models of CML through expression of the BCR/ABL oncogene in the hematopoietic system of laboratory mice. Despite numerous attempts, an accurate transgenic mouse model of CML has not been produced, possibly because of the toxicity of BCR/ABL. Conditional transgenic mice are a promising new approach to this problem. A more successful strategy is retroviral transduction of BCR/ABL into mouse bone marrow in vitro, followed by transplantation into syngeneic or immunodeficient recipient mice. Recipients of marrow transduced with p210 BCR/ABL develop a fatal myeloproliferative illness that closely resembles human CML. This model is being used to define the signaling pathways required for leukemogenesis by BCR/ABL, and for developing new therapeutic approaches.
慢性粒细胞白血病（CML）模型已被证明对于加深我们对这种疾病分子病理生理学的理解具有不可估量的价值。将原发性人类CML细胞异种移植到免疫缺陷小鼠体内，可以研究这种白血病中最原始的再增殖细胞的性质，但该系统受到变异性和实验操作难度的限制。因此，人们投入了大量精力通过在实验室小鼠的造血系统中表达BCR/ABL癌基因来开发CML模型。尽管进行了多次尝试，但尚未产生准确的CML转基因小鼠模型，这可能是由于BCR/ABL的毒性所致。条件性转基因小鼠是解决这个问题的一种有前景的新方法。一种更成功的策略是在体外将BCR/ABL逆转录病毒转导到小鼠骨髓中，然后移植到同基因或免疫缺陷受体小鼠体内。用p210 BCR/ABL转导的骨髓受体发生致命的骨髓增殖性疾病，与人类CML非常相似。该模型正用于确定BCR/ABL白血病发生所需的信号通路，并用于开发新的治疗方法。
