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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several proto-oncogenes have been reported to be expressed in normal and malignant hematopoietic cells. Since these studies have been done almost exclusively by Northern and dot-blot analyses using mixed populations of cells, any conclusions concerning quantitative changes in gene expression are difficult to document. We have developed a rapid and sensitive RNA-in situ hybridization technique permitting detection of as few as 5 copies of mRNA per individual cell. Using this technique we have studied the expression levels of several oncogenes including MYC, SIS, FMS, p53, FOS and RAF in both normal hematopoietic cells and bone marrow (BM) cells obtained from acute myelogenous leukemia (AML) patients at presentation, at relapse and in complete remission (CR). Two of these oncogenes, MYC and SIS, are expressed at levels at least 2-5-fold higher in hematopoietic cells obtained from leukemia patients than in any normal hematopoietic cell examined, including cells obtained from regenerating bone marrow. The proportion of abnormal cells correlated well with the percentage of blast cells determined by morphological examination. In 7 out of 10 AML patients in morphological remission, a subpopulation of cells is detectable with abnormally high levels of MYC and/or SIS mRNA. These high levels of MYC expression are similar to those found in BM cells obtained from AML patients at presentation or relapse, but the percentage of cells with this abnormality is generally much lower. Continued follow-up of these patients has shown that 5 of them relapsed within 8 months. At this time, none of the 3 patients which were negative for MYC overexpression has relapsed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Detection of minimal residual disease in acute myelogenous leukemia by RNA-in situ hybridization. 265 88

Enhanced expression of the human SIS/PDGF-2 gene has been reported in a number of human cell lines, sarcomas, and glioblastomas. We have analyzed the SIS/PDGF-2 gene for structural alterations in fresh human tumors. DNA samples from 79 patients with solid tumors (63 mesenchymal tumors, 12 lung carcinomas, 4 breast carcinomas) were examined and compared with DNA samples from 50 leukemia patients and 14 unrelated individuals without malignant neoplasms. When DNA samples were digested with a HindIII restriction endonuclease, Southern blot analysis demonstrated two distinct bands (21kb and 18kb) after hybridization to the SIS/PDGF-2 gene probe. A pedigree analysis of a 43-member family indicated that these allelic variants segregated in a Mendelian fashion. There was, however, tumor specific allele loss in 18% of the mesenchymal tumors analyzed, which may indicate a common etiology for this tumor type.
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PMID:Reduction to homozygosity at the SIS/PDGF-2 locus in human mesenchymal tumors. 290 34

A comparative study on the expression of nuclear and cytoplasmic oncogenes was carried out using the Northern blotting technique, in Rauscher virus induced primary leukemias and the more malignant transformed cell lines derived from them. The latter grow permanently in vitro. Hyperplastic spleens obtained from mice recovering from anemia were analysed as controls. In addition to the detection of mRNAs, Southern blotting was carried out to observe whether rearrangement or amplification of oncogenes had occurred. The results show that the nuclear oncogenes c-myc, c-myb and p53 are strongly expressed in leukemic tissue, whereas c-fos transcripts show a much weaker hybridization. The expression of two of these oncogenes, c-myc and c-myb was followed during differentiation in myeloid leukemic cells and showed a gradual decrease when compared with the actin gene, which is constitutively transcribed. A large number of cytoplasmic oncogenes is expressed in the leukemic cells lines, i.e. c-abl, c-fms, c-fes, c-src, c-ros, c-H-ras, c-K-ras and N-ras. Of these, transcripts coding for c-abl and c-src were absent in blast cells of acute erythroid leukemias. Transcripts coding for c-erb, c-mos and c-sis could also not be detected. A number of putative oncogenes which are reported to play a role in Moloney and Friend virus induced leukemias for instance pim-1, fis-1, fim-1 and fim-2 were also used for screening. Only expression of pim-1 in Rauscher virus induced myeloid leukemic cells and in primary acute erythroid leukemias could be observed. At the DNA level no rearrangement or amplification of any of the oncogenes investigated could be detected. The results show that a number of oncogenes are expressed simultaneously in the same leukemic tissue or cell lines. It therefore seems likely that the presence of transcripts of different oncogenes is associated with the progression of leukemia, but is not the primary cause of leukemogenesis or of the transformation of these cells into established cell lines.
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PMID:Oncogene expression in Rauscher murine leukemia virus induced erythroid, myeloid and lymphoid cell lines. 291 75

The c-sis gene expression in leukemia cells from a patient with acute megakaryoblastic leukemia and Down's syndrome was studied. The leukemia blasts were identified as megakaryoblasts by the platelet peroxidase reaction and the reactivity against antiplatelet monoclonal antibodies. Leukemia cells obtained from peripheral blood or bone marrow specimens before and after initiation of chemotherapy were analyzed for c-sis gene expression by the RNA-DNA dot blot hybridization. Although the level varied, the mRNA of the c-sis gene was detected in all megakaryoblastic leukemia cells obtained at different clinical stages. The c-sis mRNA level in cells obtained after relapse was higher than that obtained before the initiation of therapy. The 25S c-sis mRNA was detected in a megakaryoblastic leukemia cell line established from this patient. The role of the expression of the c-sis gene in acute megakaryoblastic leukemia cells is discussed.
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PMID:The c-sis gene expression in cells from a patient with acute megakaryoblastic leukemia and Down's syndrome. 295 17

The Philadelphia (Ph) chromosome in leukemia is invariably derived from chromosome #22. A break occurs in the long (q) arm of chromosome #22 and, in every case observed until now, all of the material from that breakpoint through the telomere of chromosome #22 has been reciprocally translocated to another chromosome, most often chromosome #9. With the t(9;22) translocation, the oncogene c-sis moves from chromosome #22 onto 9q and the oncogene c-abl moves reciprocally from chromosome #9 onto 22q. We report a new mechanism for the genesis of the Ph chromosome in chronic myelocytic leukemia (CML) involving interstitial deletion of chromosome #22 with insertion of the deleted material into another chromosome: 46,XX,dir ins(11;22)(q13;q11q13). The distal portion of chromosome #22, including the telomere, appeared to have been retained in the Ph chromosome. There was no visible involvement of chromosome #9. This insertional deletion is of potential importance in evaluating the roles of oncogenes such as c-abl and c-sis in the Ph rearrangement in the origin of leukemia.
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PMID:The Philadelphia (Ph) chromosome in leukemia. I. A new mechanism due to interstitial deletion and insertion in chronic myelocytic leukemia. 298 Nov 54

Mlvi-1 defines a genetic locus representing a common domain for proviral DNA integration in Moloney murine leukemia virus-induced rat thymic lymphomas. Cellular sequences homologous to Mlvi-1 are present in mouse DNA, and we have used hamster-mouse somatic cell hybrids to chromosomally map Mlvi-1 in the mouse genome. Results demonstrated that Mlvi-1 maps to mouse chromosome 15 and that it is distinct from the Mlvi-2 integration region and from the cellular oncogenes c-myc and c-sis, which also map to this chromosome. Therefore, Mlvi-1 may contain novel sequences involved in the establishment and maintenance of virus-induced murine tumors, many of which contain abnormalities of chromosome 15.
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PMID:Genetic mapping of a cellular DNA region involved in induction of thymic lymphomas (Mlvi-1) to mouse chromosome 15. 298 74

This study reports the immunohistological detection of serum antibody reacting with the basal aspect of syncytiotrophoblast of human chorionic villi, where SSAV/GaLV (simian sarcoma associated virus/gibbon ape lymphoma virus) type C retrovirus p30 related antigen was observed by an indirect immunofluorescent method using monospecific antibodies against SSAV p28 and GaLV p29. The immunoglobulin class of this antibody activity called 'the anti-basal aspect of syncytiotrophoblast (anti-BAST)', was exclusively IgM and detected in the sera of both female and male patients with SLE and other autoimmune diseases, but rarely in the sera of normal controls. Immunofluorescent absorption and blocking test revealed that anti-BAST specifically reacted with human placenta and cross-reacted with subhuman primate type C RNA retrovirus SSV/SSAV (simian sarcoma virus/simian sarcoma associated virus), but did not cross-react with ATLV (adult T cell leukaemia virus) and BaEV (baboon endogenous retrovirus). These results suggest the presence of a new antigen-antibody system for another human type C retrovirus related antigens(s) and a participation of retrovirus in autoimmune diseases.
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PMID:Serum antibody reacting with placental syncytiotrophoblast in sera of patients with autoimmune diseases--a possible relation to type C RNA retrovirus. 299 Jul 81

Dsi-1 is a region of chromosomal DNA that underwent proviral insertion in 3 of 24 Moloney murine leukemia virus-induced rat thymomas. In one of these tumors, a provirus is also integrated adjacent to the proto-oncogene c-myc. The proviruses in Dsi-1 have been characterized and appear to be complete. The proviruses were located within a 2-kilobase region that contained four prominent DNase I-hypersensitive sites. These hypersensitive sites were observed in Moloney murine leukemia virus-induced thymomas but not in NRK cells. The region of Dsi-1 immediately 3' to the insertions cross-hybridized with human and chicken DNA, indicating that it contains highly conserved sequences. No evidence could be found for the expression of this highly conserved region. Dsi-1 was mapped to mouse chromosome 4. This location demonstrates that Dsi-1 is different from 16 of the known proto-oncogenes (c-abl, c-erbA c-erbB, c-ets-1, c-ets-2, c-fes, c-fos, c-myb, c-myc, c-raf, A-raf, c-Ha-ras, c-Ki-ras, N-ras, c-sis, and c-src) and 12 cellular regions of tumor-associated integrations in retrovirus-induced tumors (c-erbB, Fis-1, int-1, int-2, Mis-1/pvt-1, Mlvi-1, Mlvi-2, c-mos, c-myb, c-myc, Pim-1, and c-Ha-ras). Hybridization experiments indicated that Dsi-1 is probably different from five additional proto-oncogenes (c-fgr, c-fms, c-mos, neu, and c-yes) and from two additional frequent integration regions (lck and Mlvi-3).
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PMID:Dsi-1, a region with frequent proviral insertions in Moloney murine leukemia virus-induced rat thymomas. 302 11

A probe derived from the 3' region of the BCR gene (breakpoint cluster region gene) detects four distinct loci in the human genome. One of the loci corresponds to the complete BCR gene, whereas the others contain a 3' segment of the gene. After HindIII cleavage of human DNA, these four loci are detected as 23-, 19-, 13-, and 9-kilobase-pair fragments, designated BCR4, BCR3, BCR2, and BCR1, respectively, with BCR1 deriving from the original complete BCR gene. All four BCR loci segregate 100% concordantly with human chromosome 22 in a rodent-human somatic cell hybrid panel and are located at chromosome region 22q11.2 by chromosomal in situ hybridization. The BCR2 and BCR4 loci are amplified in leukemia cell line K562 cells, indicating that they fall within the amplification unit that includes immunoglobulin lambda light chain locus (IGL) and ABL locus on the K562 Philadelphia chromosome (Ph1); additionally, in chronic myelogenous leukemia-derived mouse-human hybrids retaining a Ph1 chromosome in the absence of the 9q+ and normal chromosome 22, BCR2 and BCR4 loci are retained, whereas the 3' region of BCR1 and the BCR3 locus are lost, indicating that BCR3 is distal to BCR1 on chromosome 22. Similarly, in mouse-human hybrids retaining a Ph1 chromosome derived from an acute lymphoblastic leukemia-in the absence of the 9q+ and 22, only BCR2 and BCR4 loci are retained, indicating that the breakpoint in this acute lymphoblastic leukemia, as in chronic myelogenous leukemia, is proximal to the BCR1 3' region, but distal to the IGLC locus and the BCR2 and BCR4 3' loci. Thus, the order of loci on chromosome 22 is centromere----BCR2, BCR4, and IGL----BCR1----BCR3----SIS, possibly eliminating BCR2 and BCR4 loci as candidate targets for juxtaposition to the ABL gene in the acute lymphoblastic leukemia Ph1 chromosome.
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PMID:Mapping of four distinct BCR-related loci to chromosome region 22q11: order of BCR loci relative to chronic myelogenous leukemia and acute lymphoblastic leukemia breakpoints. 311 59

Platelet-derived growth factor (PDGF), a potent mitogen for mesenchymal cells, consists of PDGF-1 and PDGF-2 polypeptide chains which are linked by disulfide bonds. Sequence analysis has revealed that: (a) the PDGF-2 chain is encoded by the c-sis protooncogene, the cellular counterpart of the simian sarcoma viral oncogene; (b) the PDGF-1 and PDGF-2 chains are related; and (c) the PDGF-1 gene has no known viral homologue. We have previously shown that the PDGF-2 gene is expressed during 12-O-tetradecanoylphorbol-13-acetate (TPA) induced monocytic differentiation of human HL-60 leukemia cells. In the present study, PDGF-1 and PDGF-2 gene expression was compared in HL-60 cells, human THP-1 monocytic leukemia cells, and human monocytes. Uninduced HL-60 cells, uninduced THP-1 cells, and resting monocytes had no detectable PDGF-1 or PDGF-2 mRNA. In contrast, both PDGF-1 and PDGF-2 transcripts were detected in HL-60 cells and monocytes induced with TPA, while only PDGF-1 mRNA was found in TPA-treated THP-1 cells. Moreover, neither of these transcripts were found during drug induced granulocytic differentiation of HL-60 cells. Cycloheximide, an inhibitor of protein synthesis: (a) failed to increase PDGF-1 and PDGF-2 mRNA levels in uninduced HL-60 cells; (b) increased PDGF-2, but not PDGF-1, mRNA in resting monocytes; and (c) increased levels of PDGF-1 and PDGF-2 mRNA in HL-60 cells and monocytes treated with TPA. This effect of cycloheximide was related in part to stabilization of both transcripts. Thus, PDGF-1 and PDGF-2 genes are differentially regulated in myeloid cells, although they share common control mechanisms at the post-transcriptional level. Differential regulation of PDGF gene expression would result in altered chain composition of the PDGF protein and possibly changes in biological activity.
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PMID:Expression of the platelet-derived growth factor 1 and 2 genes in human myeloid cell lines and monocytes. 316 51


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