Amari N M, Kamiura S, Meruelo D
Department of Pathology, New York University Medical Center, NY 10016.
Immunogenetics. 1990;32(4):252-62. doi: 10.1007/BF00187096.
Our laboratory has focused on defining, localizing, and understanding the mode of action of genes involved in fractionated x-irradiation (FXI) leukemia in susceptible and restraint mouse strains. We have described the genetic and molecular evidence suggesting the existence of multiple independent loci involved in FXI-induced leukemogenesis. These studies indicated that one of these, Ril-1, a locus on the distal portion of chromosome 15, is the major locus influencing susceptibility to the disease. Our data unequivocally place Ril-1 in the gene complex Ly-6--Ril-1--Sis--H-30--Pol-5. Ril-1 appears to be closest to Ly-6 and Sis. We report that in FXI-induced leukemias there are hypomethylation changes in the Ly-6 region as compared to normal thymocytes. In contrast, Sis was found to be hypermethylated and not expressed. In addition, we have noted DNA rearrangements in the Ly-6--Pol-5 region in the majority of tumors examined using the Ly-6 and spleen focus-forming virus (SFFLV) molecular probes. Increased expression of Ly-6 and other surface markers encoded in this region has been noted in FXI-induced thymomas.
我们的实验室一直专注于确定、定位并理解在易患和受限制小鼠品系中参与分次X射线照射（FXI）白血病的基因的作用模式。我们已经描述了遗传和分子证据，表明存在多个参与FXI诱导白血病发生的独立基因座。这些研究表明，其中一个基因座Ril-1，位于15号染色体远端，是影响对该疾病易感性的主要基因座。我们的数据明确将Ril-1定位在基因复合体Ly-6--Ril-1--Sis--H-30--Pol-5中。Ril-1似乎最接近Ly-6和Sis。我们报告，与正常胸腺细胞相比，在FXI诱导的白血病中，Ly-6区域存在低甲基化变化。相反，发现Sis发生了高甲基化且不表达。此外，我们使用Ly-6和脾集落形成病毒（SFFLV）分子探针在大多数检测的肿瘤中发现了Ly-6--Pol-5区域的DNA重排。在FXI诱导的胸腺瘤中，已注意到该区域编码的Ly-6和其他表面标志物的表达增加。
