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)

We characterized retrovirus-induced changes in PC-12 cell function and neuronal differentiation. PC-12 cells were infected with a neurotropic retrovirus (temperature-sensitive Moloney murine leukemia virus, mutant BA-1). We isolated a cell clone from this infected culture that displayed altered response to nerve growth factor; increased choline acetyltransferase activity; and decreased basal and nerve growth factor-stimulated acetylcholinesterase activity. In addition, Kirsten murine sarcoma virus infection of and subsequent expression of the v-ras oncogene in PC-12 cells induced neurite extension, enhanced choline acetyltransferase activity, and limited the growth potential of the infected cells.
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PMID:Altered cellular functions in a PC-12 cell clone chronically infected with retrovirus. 302 28

Clonal, antigen-specific, functionally responsive cell populations have proved critical for the analysis of the activation and regulation of lymphocytes. Such studies with B lymphocytes, the precursors of antibody-secreting cells, are hampered by the difficulty in generating phenotypically mature, antigen-reactive lines from defined cell populations. One method is to use acutely transforming retroviruses, which can transform B-lineage lymphocytes in vitro. However, Abelson murine leukaemia virus (A-MuLV) infection of murine bone marrow cells in vitro yields mostly immature B-cell lines, and infection of murine bone marrow cells with murine sarcoma viruses carrying ras related genes produces only immature lymphoid cell lines. Retroviruses which contain ras can immortalize nonlymphoid cells without causing loss of mature phenotypic characteristics. We used ras-containing Kirsten sarcoma virus (KiSV) pseudotyped with an amphotropic MuLV helper virus, to infect a purified population of mature, hapten-binding murine splenic B lymphocytes, aiming to generate mature B-cell lines to use as models for the study of B-cell growth and differentiation physiology. Immortalized B-cell lines which retain the same mature phenotype as the starting population, including hapten-specific binding, were produced. This is the first demonstration of a method for immortalizing selected antigen-binding B lymphocytes, and the first example of immortalization of mature B cells in vitro with an acutely transforming ras-containing retrovirus.
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PMID:Mature murine B lymphocytes immortalized by Kirsten sarcoma virus. 302 15

AKR mice develop thymomas spontaneously when greater than 6 months old but when young AKR mice are treated with N-methyl-N-nitrosourea (MNU) they develop thymomas at 3-6 months of age. In this study the potential role of oncogene activation in the development of both the spontaneous and MNU-induced thymomas in AKR mice has been examined by DNA transfection into NIH3T3 mouse fibroblasts and by Southern analysis of tumour DNA. The results show that a high proportion of MNU-induced thymomas contain activated cellular rasK while no activated cellular ras genes were detected in spontaneous thymomas. Southern analysis of tumour DNA revealed that 2/30 spontaneous tumours and 2/52 MNU-induced tumours contained alterations in the c-myc gene while 5/29 spontaneous tumours and 6/56 MNU-induced tumours contained alterations in the Pim-1 gene. A more detailed analysis of the Pim-1 gene demonstrated that the alterations observed in most MNU-induced and spontaneous tumours resulted from proviral integration at the 3' end of this gene. Our analyses also demonstrated that the majority of MNU-induced tumours, including those containing rearrangements in the Pim-1 gene, lacked the somatically acquired recombinant MCF proviruses that are present in most spontaneous AKR lymphomas. These results provide evidence that the mechanisms of development of MNU-induced and spontaneous tumours in AKR mice are distinct and the development of thymomas that contain proviral integrations at the Pim-1 locus in the MNU-treated AKR mice involve cooperation between the chemical carcinogen and endogenous murine leukaemia viruses.
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PMID:Induction of thymomas by N-methyl-N-nitrosourea in AKR mice: interaction between the chemical carcinogen and endogenous murine leukaemia viruses. 302 78

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 murine helper/inducer T cell clone, D10.G4, has been infected with Kirsten-murine sarcoma virus (KiSV) pseudotyped with an amphotropic murine leukemia virus. The resultant Ki-ras-expressing lines (KiSV-D10) remain dependent on exogenous factors for continued growth but display distinctly different mitotic responses to certain cytokines as compared to the uninfected parent clone. Unlike the parent D10.G4 cells, these KiSV-D10 cells can be maintained in vitro indefinitely in the presence of recombinant interleukin 2 (IL 2), and they all display a maximal proliferative response to purified or recombinant interleukin 1 (IL 1). The IL 1-induced proliferation is shown not to be dependent or secretion of the T cell autocrine growth factors IL 2 or B cell stimulatory factor-1 (BSF-1). The KiSV-D10 lines show certain differences from one another and parent D10.G4 cells in their secretory and proliferative responses to T cell receptor- and BSF-1 mediated signals. These viral oncogene-expressing T cell lines, which remain responsive to and dependent on physiologic growth factors, should prove valuable for analyzing the mechanisms of action of single oncogenes and the intracellular events in T lymphocyte activation.
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PMID:Retrovirus infection alters growth factor responses of T lymphocytes. 303 71

A murine sarcoma virus (MSV) was recovered from an (NFS X NS.C58v-1) F1 mouse which developed splenic sarcoma and erythroleukemia 6 months after inoculation with a mink cell focus-inducing murine leukemia virus (MuLV) isolated from an NFS mouse infected with a wild mouse ecotropic MuLV. The MSV, designated NS.C58 MSV-1, induced foci of transformation in mouse and rat fibroblasts, and inoculation of mice of various strains 2 weeks of age or younger resulted in erythroleukemia and sarcomatous lesions in spleen, lymph node, and brain. The MSV provirus was molecularly cloned from a genomic library prepared from transformed non-producer rat cells. The 8.8-kilobase proviral DNA contained a 1.0-kilobase p21 ras coding segment which replaced most of the gp70-encoding portion of an MuLV, most likely the endogenous C58v-1 ecotropic virus. The ras oncogene is closely related to v-Ha-ras by hybridization, expression of p21 protein, and nucleotide sequence. It is nearly identical in sequence to v-bas, the only previously described transduced, activated mouse c-ras. At position 12 in the p21 coding region, arginine is substituted for the naturally occurring glycine present in c-ras. A second MSV isolate is described which is similar to NS.C58 MSV-1 except for a 100- to 200-base-pair deletion in the noncoding region of the ras-containing insert.
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PMID:Biologic and molecular characterization of two newly isolated ras-containing murine leukemia viruses. 303 12

The close association of human papillomavirus type 16 DNA with a majority of cervical carcinomas implies some role for the virus in this type of cancer. To define the transforming properties of HPV-16 DNA in vitro we have now performed transfection experiments on baby rat kidney cells using HPV-16 DNA in conjunction with an activated ras gene. We have demonstrated that a 6.6-kb DNA fragment, containing the early genes of HPV-16 under the control of Moloney murine leukaemia virus long terminal repeats (MoMuLV-LTRs), cooperates with EJ-ras in transforming these cells. Both DNAs are required and neither alone is effective. The cooperating activity appears to reside in a protein or proteins derived from the E6/E7 region of the HPV-16 genome.
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PMID:Human papillomavirus type 16 DNA cooperates with activated ras in transforming primary cells. 303 34

Three cases of idiopathic myelofibrosis were screened for the presence of mutations at codon 12, 13, or 61 of the ras gene family by a rapid method based on polymerase chain reaction and hybridization to mutation-specific oligonucleotides. PB cells of one patient showed a point mutation at codon 12 of the N-ras oncogene. This molecular genetic hallmark was used to investigate the clonal relationship of different cell lineages by cell separation analysis. Presence of the N-ras 12 mutation in granulocytes, monocytes, B cells, and T lymphocytes, as well as erythroblasts, indicates that idiopathic myelofibrosis originates from a pluripotent stem cell, at least in this patient.
Leukemia 1988 Oct
PMID:Evidence for pluripotent stem cell origin of idiopathic myelofibrosis: clonal analysis of a case characterized by a N-ras gene mutation. 305 Feb 94

DNAs from chronic granulocytic leukaemia (CGL) and chronic myelomonocytic leukaemia (CMML) were assayed for transforming genes by transfection into NIH 3T3 cells. Foci DNA was tagged with a geneticin-resistance cosmid, then followed through a drug selection and tumorigenicity assay. Activated Ha-ras genes, with point mutations at codon 12 (glycine to valine) were subsequently detected. The mutation was detected in the original samples by either MspI/HpaII digestion or polymerase chain reaction (PCR). Although mutations in the ras gene family may occur frequently in leukaemias, these are the first examples of Ha-ras mutations in CGL (blast crisis) and CMML.
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PMID:Activation of Ha-ras in human chronic granulocytic and chronic myelomonocytic leukaemia. 305 70

The influence of interferon-alpha 2 (IFN-alpha 2) on the mRNA levels of cellular proto-oncogenes was studied in malignant cells from patients with chronic lymphocytic leukemia (CLL). These cells can be induced to blast transform, differentiate and, in some cases, proliferate upon exposure to IFN. Treatment with IFN-alpha enhanced the levels of c-myc mRNA in malignant cells from the patients, whereas the levels of c-myb mRNA decreased, as measured by slot blot hybridizations. In cells from some patients, an enhanced expression of c-fos and k-ras was observed following exposure to IFN-alpha. No major effect on the expression of c-raf or of enolase was observed in any of the patients following exposure to IFN-alpha, whereas the levels of beta 2-microglobulin mRNA increased. In contrast to the observed effects on oncogene expression in CLL cells, IFN had no major effect on the expression of any of the tested oncogenes in lymphocytes from healthy donors or in B-cells from three neoplastic cell lines (380, FL18, RS). We conclude that IFN-alpha can enhance or repress the expression of several oncogenes in nondividing primary malignant cells from patients with leukemia. We also show that the response of malignant cells from patients to IFN-alpha is different than that seen with neoplastic cell lines which represent a similar stage of B-cell differentiation.
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PMID:Influence of interferon-alpha on the expression of cellular oncogenes in primary chronic lymphocytic leukemia cells. 306 Jul 97


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