Treon S P, Anand B, Chou I N, Broitman S A
Department of Microbiology, Boston University School of Medicine, MA 02118.
Leukemia. 1992;6 Suppl 3:141S-145S.
The microtubule (MT) network of the cytoskeleton has been implicated as a mediator of cellular signal transduction; disorganization of this network may allow for mitogenesis. In previous work, loss of MT network organization in human MOLT4 and HUT78 T-cell leukemias was demonstrated in contrast to an organized "spoke-wheel-like arrangement" in normal human T-lymphocytes. In this study, loss of MT network organization was shown in several representative acute myeloid leukemia (AML) cell lines: KG1 myeloblastic, HL60 promyelocytic, and U937 myelomonocytic cells. Re-organization of the MT network was observed in HL60 and U937 AML cells treated with combined lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). This re-organization paralleled earlier work which showed this combination was effective in inducing monocytic pathway differentiation and growth restraint in HL60 cells, and growth restraint in U937 cells. In contrast, KG1 cells exhibited growth restraint, but did not re-organize with LPS/TNF-alpha/IFN-gamma treatment. These results are consistent with a role for the MT network in mitogenesis. Loss of MT network organization appeared to parallel the neoplastic phenotype in three AML cell lines, whereas MT network re-organization accompanied recovery of growth control in 2 of 3 AML cell lines.
细胞骨架的微管（MT）网络被认为是细胞信号转导的介质；该网络的紊乱可能会促进有丝分裂。在先前的研究中，已证明人类MOLT4和HUT78 T细胞白血病中MT网络组织的缺失，这与正常人类T淋巴细胞中有序的“辐条轮状排列”形成对比。在本研究中，在几种代表性的急性髓性白血病（AML）细胞系中显示出MT网络组织的缺失：KG1成髓细胞、HL60早幼粒细胞和U937髓单核细胞。在用脂多糖（LPS）、肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）联合处理的HL60和U937 AML细胞中观察到MT网络的重新组织。这种重新组织与早期的研究结果相似，早期研究表明这种组合在诱导HL60细胞的单核细胞途径分化和生长抑制以及U937细胞的生长抑制方面是有效的。相比之下，KG1细胞表现出生长抑制，但在LPS/TNF-α/IFN-γ处理后没有重新组织。这些结果与MT网络在有丝分裂中的作用一致。MT网络组织的缺失似乎与三种AML细胞系中的肿瘤表型平行，而MT网络的重新组织伴随着三种AML细胞系中两种细胞系生长控制的恢复。
