Sawyers C L, Gishizky M L, Quan S, Golde D W, Witte O N
Department of Medicine, University of California-Los Angeles 90024.
Blood. 1992 Apr 15;79(8):2089-98.
Existing in vitro culture technology does not permit the routine propagation of most human myeloid leukemias. Previous work has shown the usefulness of mice with severe combined immunodeficiency (SCID) for the growth of human lymphoblastic leukemia. We show here that human myeloid cell lines and bone marrow samples from patients with acute myeloid leukemia (AML) and blast crisis of chronic myeloid leukemia (CML) also grow in SCID mice. Human AML or CML cell lines (three of three lines tested) grew in the bone marrow and peripheral blood of the mice after intravenous (IV) inoculation in a pattern closely resembling human AML. To define the best conditions for the growth of primary human myeloid leukemia cells, samples were transplanted into mice at several alternative sites. Using flow cytometry and Southern analysis, mice were analyzed at defined intervals up to 36 weeks after transplantation for the presence of human cells in various tissues. For four of four patients with AML and two of two patients with blast crisis of CML, myeloblasts grew locally at the site of implantation and were detected in the murine hematopoietic tissues. In contrast, marrow implants from patients in the chronic phase of CML (six patients) showed infrequent and limited myeloid growth in the mice. These findings demonstrate that the SCID mouse is a reproducible system for the propagation of blastic human myeloid leukemias. The differential growth of early- versus late-phase CML suggests that the SCID mouse may be a useful assay for identifying biologically aggressive leukemias early in their clinical presentation.
现有的体外培养技术无法使大多数人类髓系白血病进行常规增殖。先前的研究表明，严重联合免疫缺陷（SCID）小鼠对人类淋巴细胞白血病的生长有用。我们在此表明，来自急性髓系白血病（AML）患者和慢性髓系白血病（CML）急变期患者的人类髓系细胞系和骨髓样本也能在SCID小鼠体内生长。人类AML或CML细胞系（所测试的三个细胞系均如此）经静脉注射接种后，在小鼠的骨髓和外周血中生长，其模式与人类AML极为相似。为确定原代人类髓系白血病细胞生长的最佳条件，将样本移植到小鼠的几个不同部位。利用流式细胞术和Southern分析，在移植后长达36周的特定时间间隔对小鼠进行分析，以检测各种组织中人类细胞的存在情况。对于4例AML患者中的4例以及2例CML急变期患者中的2例，原始粒细胞在植入部位局部生长，并在小鼠造血组织中被检测到。相比之下，CML慢性期患者（6例）的骨髓植入物在小鼠体内显示出罕见且有限的髓系生长。这些发现表明，SCID小鼠是人类髓系白血病原始细胞增殖的可重复系统。CML早期与晚期的差异生长表明，SCID小鼠可能是在临床表现早期识别具有生物学侵袭性白血病的有用检测方法。
