Hebert M E, Greenberg M L, Chaffee S, Gravatt L, Hershfield M S, Elion G B, Kurtzberg J
Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710.
Transplantation. 1991 Oct;52(4):634-40. doi: 10.1097/00007890-199110000-00011.
Arabinosylguanine (araG) is a nucleoside analog that is rapidly converted by cells of the T lymphoid lineage to its corresponding arabinosylguanine nucleotide triphosphate, resulting in inhibition of DNA synthesis and selective in vitro toxicity to T lymphoblastoid cell lines as well as to freshly isolated leukemia cells from patients with T cell acute lymphoblastic leukemia. In this report, we demonstrate that araG is an effective agent to use for chemoseparation of malignant T lymphoblasts from human bone marrow. When freshly isolated human T leukemia cells or T lymphoblastoid cells were treated with 100 microM araG for 18 hr, up to 6 logs of clonogenic T cells could be eliminated without appreciable toxicity to the normal myeloid, erythroid, and megakaryocytoid clonal progenitor cells. We discuss the use of this agent in ex vivo elimination of residual malignant T cells from marrow of patients requiring myeloablative chemotherapy with autologous bone marrow rescue.
阿拉伯糖基鸟嘌呤（araG）是一种核苷类似物，T淋巴细胞系细胞可迅速将其转化为相应的三磷酸阿拉伯糖基鸟嘌呤核苷酸，从而抑制DNA合成，并对T淋巴母细胞系以及从T细胞急性淋巴细胞白血病患者新鲜分离的白血病细胞具有选择性体外毒性。在本报告中，我们证明araG是一种用于从人骨髓中化学分离恶性T淋巴母细胞的有效药物。当将新鲜分离的人T白血病细胞或T淋巴母细胞用100 microM araG处理18小时时，可消除多达6个对数的克隆形成T细胞，而对正常髓系、红系和巨核细胞系克隆祖细胞无明显毒性。我们讨论了该药物在体外清除需要进行清髓性化疗并自体骨髓挽救的患者骨髓中残留恶性T细胞的应用。
