Kelliher M A, Weckstein D J, Knott A G, Wortis H H, Rosenberg N
Department of Pathology, Tufts University School of Medicine, Boston, Massachussetts 02111.
Oncogene. 1993 May;8(5):1249-56.
Mice reconstituted with BCR/ABL-infected 5-fluorouracil-treated bone marrow are considered a model system for human chronic myelogenous leukemia, a malignancy that arises in hematopoietic stem cells. These animals develop multiple types of hematopoietic tumors, which could arise either from undifferentiated cells that mature during tumor development or from progenitors committed to different lineages. To examine the BCR/ABL-sensitive target cells present in the marrow of mice treated with 5-fluorouracil, we used a single-step in vitro assay. These experiments revealed that both the P210 and P185 BCR/ABL proteins and the related v-abl protein induce lymphoid and myeloid colonies, colony types that mimic two of the prominent types of tumors found in the reconstitution model. The lymphoid colonies were similar to lymphoid colonies found following infection of normal bone marrow with respect to differentiation state and tumorigenicity. The cells in the myeloid colonies were differentiated and non-tumorigenic. Fluorescence-activated cell sorting revealed that most of the lymphoid and myeloid colonies arose from distinct precursors and that the lymphoid colonies arose from B-lineage-committed cells. These data suggest that most of the lymphomas observed in the reconstitution model arise from committed progenitors that are distinct from those involved in the myeloid disease.
用感染了BCR/ABL的经5-氟尿嘧啶处理的骨髓重建的小鼠被视为人类慢性粒细胞白血病的模型系统，慢性粒细胞白血病是一种起源于造血干细胞的恶性肿瘤。这些动物会发生多种类型的造血肿瘤，这些肿瘤可能源于在肿瘤发展过程中成熟的未分化细胞，也可能源于定向分化为不同谱系的祖细胞。为了检测存在于经5-氟尿嘧啶处理的小鼠骨髓中的对BCR/ABL敏感的靶细胞，我们使用了一种单步体外试验。这些实验表明，P210和P185 BCR/ABL蛋白以及相关的v-abl蛋白均可诱导淋巴样集落和髓样集落，这两种集落类型类似于在重建模型中发现的两种主要肿瘤类型。淋巴样集落在分化状态和致瘤性方面与正常骨髓感染后发现的淋巴样集落相似。髓样集落中的细胞已分化且无致瘤性。荧光激活细胞分选显示，大多数淋巴样集落和髓样集落来自不同的前体细胞，且淋巴样集落来自B谱系定向细胞。这些数据表明，在重建模型中观察到的大多数淋巴瘤源自与髓系疾病相关祖细胞不同的定向祖细胞。
