O'Brien S, Jeha S, Kantarjian H, Pisa P, Jin G, Keating M, Beran M
Department of Hematology, University of Texas MD Anderson Cancer Center, Houston, USA.
Leukemia. 1996 Feb;10(2):338-44.
Engraftment of human acute leukemia cells in immunocompromised (SCID) mice has resulted in in vivo models for exploration of human tumor biology. Attempts at engraftment of chronic leukemia cells have been generally unsuccessful. We have engrafted cells from three human chronic leukemias in SCID mice. Cell populations were from two patients with chronic lymphocytic leukemia (CLL) and either increased proolymphocytes (CLL-Pro; patient 1), or prolymphocytic transformation (PLL; patient 2) and from a third patient with newly diagnosed T cell CLL. Both fresh and cryopreserved cells were used and were injected intravenously, intraperitoneally, or both, after conditioning with cyclophosphamide. In addition, cells derived from a mouse spleen engrafted with human leukemia were passaged into another mouse. The animals were observed daily for signs of disease or appearance of tumors and sacrificed when terminally ill. At intervals blood samples were obtained and analyzed for the presence of human cells or DNA. Human leukemic cells were demonstrated by polymerase chain reaction (PCR) analysis of the human DQalpha gene or positive staining for human leukocyte common antigen (LCA). The presence of Epstein-Barr virus (EBV)-positive cells was also investigated by PCR analysis. Disseminated tumors developed in most mice inoculated with cells from the first patient, and this was associated with shortened survival times. The methods of administration, use of fresh or frozen samples, or the size of the inoculum had no effect on the development of leukemia. Survival of the mouse receiving passaged cells was similar to mice inoculated with fresh cells. Extensive histologic, immunophenotypic, and DNA studies were performed on organs from mice engrafting with cells from patient 1. PCR analysis for EBV sequences was negative in the mice engrafting from all three cases. The successful engraftment of human CLL-Pro PLL and T cell CLL in SCID mice, and the reproducibility of this effect using frozen cells, will provide a model for exploration of disease biology and for investigations of new drugs or combinations that may be useful in the treatment of CLL.
将人类急性白血病细胞移植到免疫缺陷（SCID）小鼠体内，已产生用于探索人类肿瘤生物学的体内模型。移植慢性白血病细胞的尝试通常未成功。我们已将来自三例人类慢性白血病的细胞移植到SCID小鼠体内。细胞群体来自两名慢性淋巴细胞白血病（CLL）患者，其中一名患者的幼淋巴细胞增多（CLL-Pro；患者1），另一名患者发生幼淋巴细胞转化（PLL；患者2），还有一名新诊断的T细胞CLL患者。使用了新鲜细胞和冻存细胞，在用环磷酰胺预处理后，通过静脉内、腹腔内或两者联合注射。此外，将源自移植了人类白血病的小鼠脾脏的细胞传代至另一只小鼠体内。每天观察动物是否有疾病迹象或肿瘤出现，在濒死时处死。定期采集血样并分析其中人类细胞或DNA的存在情况。通过对人类DQalpha基因进行聚合酶链反应（PCR）分析或对人类白细胞共同抗原（LCA）进行阳性染色来证实人类白血病细胞的存在。还通过PCR分析研究了爱泼斯坦-巴尔病毒（EBV）阳性细胞的存在情况。大多数接种第一名患者细胞的小鼠发生了播散性肿瘤，这与生存时间缩短有关。给药方法、使用新鲜或冷冻样本以及接种物大小对白血病的发生均无影响。接受传代细胞的小鼠的生存期与接种新鲜细胞的小鼠相似。对移植了第一名患者细胞的小鼠的器官进行了广泛的组织学、免疫表型和DNA研究。对所有三例移植小鼠进行的EBV序列PCR分析均为阴性。人类CLL-Pro、PLL和T细胞CLL在SCID小鼠中的成功移植，以及使用冻存细胞这种效应的可重复性，将为探索疾病生物学以及研究可能对CLL治疗有用的新药或联合用药提供一个模型。
