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A portion of the human cellular homolog of v-rel, the transforming gene of the leukemogenic retrovirus reticuloendotheliosis virus, strain T, was used to survey RNAs from several mouse tissues, selected lymphocyte populations, and hematopoietic cell lines for c-rel expression. Relatively high levels of a high-molecular-weight transcript were observed in peripheral B and T cells, whereas lower levels were detectable in functionally immature thymocytes. These results suggested that, unlike c-myb and c-ets, the c-rel proto-oncogene plays a role in later stages of lymphocyte differentiation.REV-T, a highly leukemogenic virus of galliform birds, is believed to have arisen by recombination between a replication-competent type C retrovirus and a portion of a turkey cellular gene designated c-rel (30, 31). Evolutionary comparisons between cloned segments of the turkey and chicken c-rel homologs indicate that the rel locus resembles many other cellular proto-oncogenes in being both large and complex (6, 30). The nine exons from which v-rel was derived, for example, are dispersed over more than 20 kilobase (kb) pairs of DNA and range in size from -60 to over 500 base pairs (30). Very little is known about the normal expression of this cellular gene except that elevated levels of rel-related transcripts can be detected in avian hematopoietic tissues, suggesting a potential role for c-rel in the differentiation of lymphoid and myeloid cell lineages (6,14).Recently, we presented evidence that unique c-rel loci could also be identified in humans, mice, and cats, all of which provide potentially useful genetic model systems for studying the function of this proto-oncogene (3, 4). To date, however, no clear picture has emerged regarding c-rel transcription in any mammalian group, a problem based partly on the fact that the rel-specific probes used in previous studies were derived from the distantly related avian viral rel oncogene (19,23,25,28). In this study, we used a recently described cloned DNA fragment containing two exons of the human c-rel proto-oncogene (4) to screen RNAs from various postnatal mouse tissues, fractionated lymphocytes, and cell lines. We detected large (-7.5 kb) rel-homologous transcripts in thymic and splenic RNAs from 9-, 18-, and 28-day-old mice, whereas RNAs from kidney and liver tissues from the same mice were essentially negative in comparison. Analyses of RNA samples from fractionated lymphocytes showed high levels of rel transcripts in surface immunoglobulin-positive splenic B cells, followed closely by Lyt2-L3T4+ and Lyt2+ L3T4-splenic T lymphocytes. RNA samples from thymocyte populations obtained by differential agglutination with peanut lectin (PNA) were weakly positive, although the more mature, medullary-type PNA-fraction showed a slightly higher level of expression. We corroborated this observation by analyzing RNAs from thymocyte subsets obtained by positive selection and from * Corresponding author.various established murine lymphocyte cell lines. Judging from the elevated levels found i...

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We isolated and sequenced a human genomic-DNA segment that is homologous to a portion of v-rel, the transforming gene of reticuloendotheliosis virus (strain T). We also localized the human rel sequences to human chromosome 2 by screening a panel of rodent x human somatic-cell hybrids with the newly described human rel segment. Cellular homologs of retroviral transforming genes have been identified in birds and mammals, in which these homologs are thought to perform important roles in regulating cell proliferation and differentiation (for a review, see reference 2). Recent studies suggest, however, that specific alterations in normal cellular oncogene structure and expression may themselves initiate cellular transformation in the absence of retroviral infection (e.g., see references 7, 15, 24, and 30). Such observations have prompted investigators to clone cellular oncogene homologs to study their normal biological properties and to determine whether alterations in these properties are consistently associated with naturally occurring, nonvirally induced malignancies. In this study, we determined the nucleotide sequence and chromosomal localization of a cloned human DNA segment carrying two putative exons homologous to the transforming gene (v-rel) of reticuloendotheliosis virus strain T (REV-T). The human c-rel sequences may provide a useful tool for studying the structure and function of this cellular oncogene in mammals.REV-T is a replication-defective (11) type C retrovirus (3,12,25,36) that induces acute leukemia in young chickens and turkeys (32). It is the only known acutely transforming member (9, 10) of a retroviral family that includes spleen necrosis virus, chick syncytial virus, duck infectious anemia virus, and the REV-T helper reticuloendotheliosisassociated virus (REV-A) (11,14). The REV-T genome carries a genomic substitution of approximately 1.42 kilobases (kb) near its 3' end (4, 6, 29) that is required for cellular transformation (5). This sequence, termed v-rel, is believed to have been derived from several exons of a turkey cellular gene (4,27,35), and recent molecular analyses of the turkey c-rel locus support this hypothesis (33). We began our investigation by performing Southern transfer and hybridization experiments to determine whether v-rel homologies could also be detected in humans and other mammals. The results of one such experiment in which cellular DNAs of hamsters, mice, humans, and chickens were hybridized with Sst v-rel, a 514-base-pair (bp) subclone of v-rel, are shown in Fig. le. After a 3-day exposure, one or two rel-homologous DNA bands were noted in all of the lanes, including those containing human DNA (see also reference 4).We next used Sst v-rel to screen (1) a human partial HaeIII-AluI genomic-DNA library (18) This fragment (pPHHSrel-1) was subcloned for further sequence analysis. Additional Sst v-rel homologies could not be identified, leading us to speculate either that the phage clone carried only a small portion of the human c-rel gene or that HSrel-1 and Sst v-r...

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