Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic myelogenous leukemia (CML) is a human disease associated with a consistent chromosomal translocation that results in sequences from the c-abl locus on chromosome 9 being fused to sequences in a breakpoint cluster region (bcr) on chromosome 22. CML cells have two novel products: an 8.5-kilobase RNA transcript containing both abl and bcr and a 210-kilodalton phosphoprotein (P210) recognized by v-abl-specific antisera. To test whether the P210 is the product of the novel 8.5-kilobase bcr/abl fusion transcript, antibodies were prepared against c-abl and bcr determinants. By using these reagents and v-abl-specific antisera, it was demonstrated that the P210 in CML cells is indeed the protein product of the 8.5-kilobase transcript. By analogy to the gag/abl fusion protein of Abelson murine leukemia virus, the replacement of amino terminal c-abl sequences by bcr sequences in P210 may create a transforming protein involved in CML. A 190-kilodalton phosphoprotein that is a candidate for the normal bcr protein was identified in both HeLa and K562 cells.
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PMID:The chronic myelogenous leukemia-specific P210 protein is the product of the bcr/abl hybrid gene. 346 Jan 76

Thyroglobulin (Tg)-binding peripheral blood T cells from a normal individual were fused with a T cell leukemia cell line (Jurkat-AG9) treated by emetine and actinomycin D. Several cell lines were established from thus-prepared human T cell hybridomas. The culture supernatant from one of these lines (Tg-Ts47) whose phenotype was OKT3- 11+ 4+ 8- suppressed the generation of Tg-specific antibody-forming cells from the lymphocytes of patients with Hashimotos' chronic thyroiditis, but not anti-SRBC and anti-ovalbumin antibody production from both autologous and patient lymphocytes. Tg-Ts47-derived factors also bore Tg antigen-binding sites. The suppressive activity of the supernatants was shown in almost all patients lymphocytes tested. This indicated that the supernatants of Tg-Ts47 line contain a suppressive factor specific for Tg antigen and capable of acting across allogeneic barriers.
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PMID:Establishment of a human T cell hybridoma cell line producing suppressor factor specific for anti-thyroglobulin antibody production. 349 75

We have surveyed 22 kb of DNA from the region surrounding the human fetal (gamma) globin genes and have identified one fragment that meets all of the criteria for a non-tissue specific enhancer element. The enhancer-containing fragment starts approximately 400 bp 3' to the polyadenylation signal of the A gamma gene and is less than 750 bp in length. Addition of this fragment to plasmids containing a 'gamma-CAT' hybrid gene [consisting of the gamma globin gene promoter fused to the chloramphenicol acetyl transferase (CAT) gene] increases CAT expression 6-23-fold in K562 erythroleukemia cells, depending upon the method of transfection. The increase in expression is essentially independent of the orientation or position of the fragment with respect to the gamma-CAT hybrid gene. The 3' gamma enhancer activates heterologous promoters in erythroleukemia cells, and is also active in non-erythroid cell lines. The enhancer acts by increasing the number of transcripts initiated from the normal gamma globin gene transcription initiation site. The enhancer region contains two DNase I hypersensitive sites in erythroleukemia cells but none in nonerythroid human leukemia cell lines. The 3' gamma globin gene enhancer contains a unique element that is similar to sequences found in an enhancer 3' to the chicken beta globin gene, suggesting that this conserved element may have a role in enhancer function.
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PMID:An enhancer element lies 3' to the human A gamma globin gene. 369 78

Deletional analysis within the long terminal repeat (LTR) of Moloney murine leukemia virus (M-MuLV) was performed. By molecular cloning, deletions were made in the vicinity of the XbaI site at -150 base pairs (bp) in the U3 region, between the tandemly repeated enhancers and the TATA box. The effects of the deletions on LTR function were measured in two ways. First, deleted LTRs were fused to the bacterial chloramphenicol acetyltransferase gene and used in transient expression assays. Second, infectious M-MuLVs were generated by transfection of M-MuLV proviruses containing the deleted LTRs, and the relative infectivity of the mutant viruses was assessed by XC-syncytial assay. Most of the deleted LTRs examined showed relatively high promoter activity in the transient chloramphenicol acetyltransferase assays, with values ranging from 20 to 50% of the wild-type M-MuLV LTR. Thus, the sequences between the enhancers and the TATA box were not absolutely required for transient expression. However, infectivity of viruses carrying the same deleted LTRs showed more pronounced effects. Deletion of sequences from -195 to -174 bp reduced infectivity 20- to 100-fold. Deletion of sequences within the region from -174 to -122 bp did not affect infectivity, indicating that this region is dispensable. On the other hand, deletion of sequences from -150 to -40 bp reduced infectivity from 5 to 6 logs, although the magnitude of the reduction partly may have reflected threshold envelope protein requirements for positive XC assays. The reduced infectivity did not appear to result from a failure of proviral DNA synthesis or integration by the mutant. Thus, the infectivity measurements identified three functional domains in the region between the enhancers and the TATA box.
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PMID:Generation of infectious Moloney murine leukemia viruses with deletions in the U3 portion of the long terminal repeat. 379 12

We have recently described that a variant of L1210 leukemia cell (L1210/LN-1) originally fused with Lesch-Nyhan fibroblast is highly immunogenic for inducing tumor-specific transplantation immunity in (BALB/cxDBA/2)F1 mice. This finding has clearly been confirmed in the present study by in-vitro cell-mediated cytotoxicity assay. Direct cytotoxic tests and competitive inhibition tests using tumor cells such as P388, LS-1 and L5178Y as target or inhibitor cells showed that the cell-mediated immunity is specific to L1210 leukemia. In the process of this study, we found that the CD2F1 mice hyperimmune to L1210 leukemia cells developed co-existing humoral anti-L1210 leukemia immunity. In an in vitro complement-dependent cytotoxicity test and absorption test, antisera from hyperimmune mice reacted specifically to L1210 leukemia cells, but not other tumor cells such as P388, L5178Y, LS-1, DB27C and BW5147 or normal cells from various tissues of DBA/2, BALB/c and AKR mice. In an in vitro cytotoxicity blocking test, the cytotoxic antisera specifically reactive to L1210 cells totally failed to inhibit lysis of L1210 cells by cytotoxic cells, suggesting that antigens recognized by cell-mediated cytotoxicity assays are not identical to serologically defined tumor-cell surface antigens.
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PMID:Simultaneous development of humoral and cellular tumor-specific immunity against L1210 mouse leukemia. 402 40

A series of 5-[(aminoalkyl)amino]-substituted anthra[1,9-cd] pyrazol-6(2H)ones (anthrapyrazoles) were synthesized. These compounds, which differ from the anthracenediones in that an additional pyrazole ring has been fused to the anthracene system in place of one carbonyl group, were evaluated in vivo for their anticancer activity in eight different mouse tumor systems. Compounds were selected for testing primarily on the basis of their high levels of activity P388 leukemia and occasionally for structural considerations. Sixty-seven % of the 21 analogues studied were curative in the National Cancer Institute P388 screen. Many of the compounds tested were highly active against each of the tumors of the National Cancer Institute panel. Thus 82, 73, 45, and 80% of the compounds tested were curative for L1210 leukemia, B16 melanoma, M5076 sarcoma, and the MX-1 mammary xenograft, respectively. Several of the compounds studied were curative against every tumor of the above panel. Because of the high activity of the anthrapyrazole series as a class in the National Cancer Institute tumor panel, additional testing was necessary to allow selection of clinical candidates. Twenty-one anthrapyrazoles were tested against mammary adenocarcinoma 16C, colon adenocarcinoma 11a, and the Ridgway osteogenic sarcoma. Four compounds, PD 113,309 (Cl-937), PD 113,785 (Cl-941), PD 111,815 (Cl-942), and PD 115,593, were judged superior to the rest on the basis of the expanded panel testing. The preclinical data to date suggest that these anthrapyrazoles are similar to doxorubicin in both degree and spectrum of activity. Each of these anthrapyrazoles were significantly more active than were the other synthetic intercalating agents, the anthracenediones mitoxantrone and ametantrone, against the tumors of the expanded panel. On the basis of their high level of broad spectrum activity in preclinical systems, ease of formulation, possible lack of cross-resistance with doxorubicin, and potential lack of cardiotoxicity, Cl-937, Cl-941, and Cl-942 have been selected for further preclinical evaluation and possible clinical development.
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PMID:Anthrapyrazoles, a new class of intercalating agents with high-level, broad spectrum activity against murine tumors. 405 27

We have studied the DNA sequences required for high-level expression of a cloned chicken alpha-crystallin gene by introducing a hybrid alpha/delta-crystallin gene into nuclei of mouse lens epithelial cells in primary culture. The level of transient expression of the hybrid gene consisting of the 5' upstream promoter region of the alpha-crystallin gene fused to the structural portion of the delta-crystallin gene was determined by Western blot analysis using anti-delta-crystallin serum. The hybrid gene appears to be expressed in a tissue-specific manner, since it is active in mouse lens cells but not in fibroblasts or in L cells. The DNA sequences located 242-189 bp upstream from the transcription initiation site are required for high-level expression in lens cells. They are active when their orientation is reversed at the original site or when placed approximately 1.7 kbp downstream from the cap site in the second intron of the hybrid gene in either orientation. When these DNA sequences were replaced by the enhancer sequences of Moloney murine leukemia virus, the hybrid gene was expressed in both lens cells and fibroblasts.
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PMID:DNA sequences responsible for tissue-specific expression of a chicken alpha-crystallin gene in mouse lens cells. 405 99

Cultures of human cells nonpermissive for mouse leukemia virus replication could not be induced to support virus replication by homologous fusion in the presence of Moloney leukemia virus. Human cells were also fused with permissive mouse cells, and the fate of the virus in heterokaryons was determined by a simultaneous autoradiography and fluorescent antibody technique. Heterokaryons containing the full chromosome complement of both cells were likewise nonpermissive for virus synthesis, but hybrids of human and mouse cells, which lacked up to half of the human chromosome complement, were permissive for virus synthesis. The results suggest that human cell genes can direct a repressive control over mouse leukemia virus replication.
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PMID:Murine leukemia virus: restriction in fused permissive and nonpermissive cells. 434 78

The C-type particles produced by the A9 and A9HT sublines of mouse L cells were shown to infect C3H (N type), but not C57BL (B type), mouse embryo fibroblasts. Infection was indicated by distinct single giant cell formation in the XC monolayer used to overlay the mouse embryo fibroblasts. On the basis of these results it was concluded that the L cell virus is N tropic. A9 and A9HT cells were fused to various mouse cells derived from tumors and normal tissues. The ability to produce the Moloney-type surface antigen and to release infectious virus was introduced by the A9 component into the hybrid cell. Virus production, measured by antigen induction on JLS-V9 cells, was suppressed in those hybrids in which the partner cell had a genotype determining low infectibility with that particular virus (B-type cell). It thus appears that the major genetic locus affecting resistance to infection with leukemia viruses, the Fv-1 locus, regulates infectious virus production in somatic cell hybrids also. The same genetic locus did not seem to govern the expression of all virus-related functions, for the virus-determined membrane antigen was demonstrated in many of the N x B-type hybrids in which production of infectious virus was suppressed.
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PMID:The influence of the partner cell on the production of L virus and the expression of viral surface antigen in hybrid cells. 434 52

The genomes of bovine leukemia and human T-cell leukemia viruses both contain an unidentified region between the gag and pol genes. These regions harbor an open reading frame that is in a different phase from the reading frames of the gag and pol genes. Based on the deduced amino acid sequences, we show here that they potentially encode a gag precursor-cleaving protease, which is known to be fused to the gag and pol products of avian and murine retroviruses, respectively. This finding raises the interesting question of the expression and evolution of retroviral genes.
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PMID:Identification of a potential protease-coding gene in the genomes of bovine leukemia and human T-cell leukemia viruses. 609 58


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