Susceptibility and resistance to Moloney murine leukemia virus-induced promonocytic leukemia.
Susceptibility and resistance to Moloney murine leukemia virus-induced promonocytic leukemia.
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对莫洛尼鼠白血病病毒诱导的早单核细胞白血病的易感性和抵抗力。
DOI：
10.1006/viro.1994.1668
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发表时间：
1994
期刊：
影响因子：
3.7
通讯作者：
L. Wolff
中科院分区：
文献类型：
--
作者：
V. Nazarov;D. Hilbert;L. Wolff
莫洛尼鼠白血病病毒（M-MuLV）在降植烷处理的成年小鼠中诱导前单核细胞白血病，称为MML。这些肿瘤总是表达融合的gag-myb mRNA作为病毒整合和c-myb基因座激活的结果。在本研究中，确定了BALB/c和DBA/2N小鼠高度易感，而C57 BL/6、C3 H/He、STS/A、NFS、NIH/Swiss、SJL/J和NZB小鼠对肿瘤诱导具有强烈抗性。尽管C57 BL/6小鼠具有抗性，因为它们不能支持造血组织中的早期病毒复制，但NFS和C3 H/He小鼠支持复制，并且使用RT-PCR显示，骨髓和脾脏中的细胞表达异常的白血病相关gag-myb mRNA。这提供了证据，表明这些小鼠中允许发展早期白血病，但癌前细胞无法进展到急性期。在免疫缺陷C3 H/He nu/nu和亚致死剂量照射C3 H/He小鼠中，M-MuLV加降植烷处理诱导MML的实验表明，免疫应答可能在消除免疫活性C3 H/He中的白血病前细胞中发挥作用。这些小鼠的肿瘤在c-myb基因座发生重排并表达gag-myb RNA。结论是，至少在C3 H/He小鼠的情况下，抗性不是由于病毒不能激活c-myb或缺乏其他肿瘤促进事件。相反，白血病的发展似乎受到免疫反应的限制，可能是T细胞介导的。证明非H-2 MHC基因是C57 BL/6和C3 H/He小鼠产生耐药性所必需的，并且耐药性是显性的。这为研究肿瘤进展提供了动物模型，因为它与免疫应答有关。
Moloney murine leukemia virus (M-MuLV) induces promonocytic leukemias, called MML, in pristane-treated adult mice. These tumors invariably express fused gag-myb mRNA as a consequence of virus integration and activation of the c-myb locus. In the present study it was determined that while BALB/c and DBA/2N mice are highly susceptible, C57BL/6, C3H/He, STS/A, NFS, NIH/Swiss, SJL/J, and NZB mice are strongly resistant to tumor induction. Although C57BL/6 mice were resistant because they were unable to support early virus replication in hematopoietic tissue, NFS and C3H/He mice supported replication and were shown, using RT-PCR, to have cells in the bone marrow and spleen that expressed the aberrant, leukemia-related gag-myb mRNA. This provided evidence that early stages of leukemia were permitted to develop in these mice, but preneoplastic cells were unable to progress to the acute phase. Experiments in which MML was induced by M-MuLV plus pristane treatment in immunodeficient C3H/He nu/nu and sublethally irradiated C3H/He mice suggested that the immune response may play a role in eliminating preleukemic cells in immunocompetent C3H/He. Tumors from these mice had rearrangements at the c-myb locus and expressed gag-myb RNA. It was concluded that, at least in the case of C3H/He mice, resistance is not due to an inability of virus to activate c-myb or to a lack of other tumor promoting events. Rather, leukemia development appears to be restricted by an immune response, presumably T-cell mediated. Evidence is provided that non-H-2 MHC genes are required for resistance in both C57BL/6 and C3H/He mice and that resistance is dominant. This provides an animal model for the study of tumor progression as it relates to the immune response.