Beyer G S, Bruno E, Hoffman R
Cancer Res. 1985 Nov;45(11 Pt 2):5921-5.
The treatment of acute nonlymphocytic leukemia results in predictable bone marrow hypoplasia and eventual cellular repopulation. In order to study this postchemotherapy repopulation, assays for hematopoietic progenitor cells were performed on bone marrow samples obtained from seven patients with acute nonlymphocytic leukemia who had received similar chemotherapeutic induction regimens. Burst-forming units (erythrocyte), colony-forming units (megakaryocyte), colony-forming units (granulocyte-macrophage), and colony-forming units (granulocyte-erythrocyte-megakaryocyte-macrophage) were cloned from human bone marrow mononuclear cells 5 and/or 10 days following completion of chemotherapy. All patients were pancytopenic and had hypocellular marrows when studied. Assays were performed 7 to 30 days prior to complete remission. Colony-forming units (granulocyte-macrophage) were equivalent to control values 5 days following chemotherapy, while burst-forming units (erythrocyte) and colony-forming units (granulocyte-erythrocyte-megakaryocyte-macrophage) were not assayable at that time. Ten days following chemotherapy, colony-forming units (granulocyte-erythrocyte-megakaryocyte-macrophage) and colony-forming units (granulocyte-macrophage) were 200 and 250% of normal controls, respectively, while burst-forming units (erythrocyte) were 29% of control values. Colony-forming units (macrophage) were 10 to 15 times normal values 10 days following chemotherapy. In contrast to colonies from normal individuals, those grown from marrow obtained following chemotherapy were frequently macroscopic and were composed of thousands of cells. Patient marrow had larger proportions of progenitor cells in S phase of the cell cycle than did normal controls. These studies suggest the presence of a stem cell in human bone marrow which is resistant to chemotherapeutic agents and has a high capacity to regenerate hematopoietic progenitor cells. The period following completion of chemotherapy for acute nonlymphocytic leukemia appears suitable for the study of the hierarchical nature of human hematopoiesis.
急性非淋巴细胞白血病的治疗会导致可预测的骨髓发育不全以及最终的细胞再增殖。为了研究化疗后的这种再增殖情况，对7例接受了相似化疗诱导方案的急性非淋巴细胞白血病患者的骨髓样本进行了造血祖细胞检测。在化疗结束后的5天和/或10天，从人骨髓单个核细胞中克隆出爆式红系集落形成单位、巨核细胞集落形成单位、粒-巨噬细胞集落形成单位以及粒-红-巨核-巨噬细胞集落形成单位。研究时所有患者均全血细胞减少且骨髓细胞减少。在完全缓解前7至30天进行检测。化疗后5天，粒-巨噬细胞集落形成单位与对照值相当，而此时爆式红系集落形成单位和粒-红-巨核-巨噬细胞集落形成单位无法检测。化疗后10天，粒-红-巨核-巨噬细胞集落形成单位和粒-巨噬细胞集落形成单位分别为正常对照的200%和250%，而爆式红系集落形成单位为对照值的29%。化疗后10天，巨噬细胞集落形成单位是正常值的10至15倍。与正常个体的集落不同，化疗后获得的骨髓所生长出的集落通常肉眼可见，且由数千个细胞组成。患者骨髓处于细胞周期S期的祖细胞比例高于正常对照。这些研究表明人骨髓中存在一种对化疗药物有抗性且具有高再生造血祖细胞能力的干细胞。急性非淋巴细胞白血病化疗结束后的这段时间似乎适合研究人类造血的层级性质。
