Torok-Storb B, Simmons P, Khaira D, Stachel D, Myerson D
Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Ann Hematol. 1992 Jun;64 Suppl:A128-31. doi: 10.1007/BF01715365.
Infection with cytomegalovirus (CMV) continues to be one of the most common complications following allogeneic bone marrow transplantation. A proportion of patients with CMV infection also experience neutropenia. To investigate the possible role of CMV in the suppression of hematopoiesis, we have examined the effect of CMV on the growth of isolated myeloid progenitors and on the production of myeloid cells in the long-term bone marrow culture (LTMC) system. In these studies, various isolates of CMV were added either directly to cultures of progenitors or to LTMC established from normal CMV-seronegative donors. In the first system, myelosuppression is manifested by a reduction in the number of colonies that grow. In the second system, myelosuppression is manifested by a reduction in the number of myeloid cells produced and released into the culture supernatant. Analysis of the data observed indicated that myelosuppression could in some cases be attributed to direct infection of myeloid progenitors. In other cases stromal cells were infected. In the latter cases, myelosuppression was then caused by an alteration in cytokines produced by the stromal cells. These observations made in vitro raise the possibility that comparable mechanisms may be responsible for the myelosuppression observed with CMV infection in vivo. To pursue this possibility we proposed to detect the CMV genome in defined subpopulations of marrow cells isolated from infected patients. Given the technical restrictions imposed by the small sample size available from patient marrow aspirations, our initial attempts to develop on appropriate technique involved isolation of cells from CMV-seropositive normal bone marrow donors. Using the polymerase chain reaction we were able to amplify CMV DNA contained within marrow cells of some healthy CMV-seropositive marrow donors.
巨细胞病毒（CMV）感染仍然是异基因骨髓移植后最常见的并发症之一。一部分CMV感染患者也会出现中性粒细胞减少。为了研究CMV在造血抑制中的可能作用，我们检测了CMV对分离的髓系祖细胞生长以及长期骨髓培养（LTMC）系统中髓系细胞产生的影响。在这些研究中，将各种CMV分离株直接添加到祖细胞培养物中，或添加到由正常CMV血清阴性供体建立的LTMC中。在第一个系统中，骨髓抑制表现为生长的集落数量减少。在第二个系统中，骨髓抑制表现为产生并释放到培养上清液中的髓系细胞数量减少。对观察到的数据进行分析表明，在某些情况下，骨髓抑制可归因于髓系祖细胞的直接感染。在其他情况下，基质细胞被感染。在后一种情况下，骨髓抑制是由基质细胞产生的细胞因子改变引起的。这些体外观察结果增加了这样一种可能性，即类似的机制可能是体内CMV感染所观察到的骨髓抑制的原因。为了探究这种可能性，我们提议检测从感染患者分离的特定骨髓细胞亚群中的CMV基因组。鉴于患者骨髓穿刺获得的样本量较小所带来的技术限制，我们最初开发合适技术的尝试涉及从CMV血清阳性的正常骨髓供体中分离细胞。使用聚合酶链反应，我们能够扩增一些健康的CMV血清阳性骨髓供体骨髓细胞中所含的CMV DNA。
