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

Neonatal infection of C57BL/10 mice with cloned ecotropic and/or dualtropic mink cell focus-inducing (MCF) mouse leukaemia viruses (MuLV), induces a wide spectrum of different lymphomas of T, B, and non-T/non-B cell types. The H-2 complex has a marked influence on both the development of lymphoma incidence and lymphoma type. A study using the oncogenic MCF 1233 virus and a series of B10 congenic mice enabled the mapping of the following: Resistance to the early development of T cell lymphoma is controlled by the H-2I-A locus. Susceptibility to early T cell lymphomagenesis is associated with an I-A-regulated low anti-MCF 1233 envelope antibody response and persistent infection of the thymus. B10 (H-2b) mice, which are resistant to early T cell lymphomagenesis induced by MCF 1233 or other MuLV isolates, have high anti-MuLV envelope antibody responses which are I-A-regulated. These mice develop more B cell lymphomas late in life in contrast to the early development of T cell lymphoma in B10.A (H-2a) mice. The possible response mechanisms which underlie these observations, including: I-A-regulated immunoselection against MuLV antigens expressed by (pre) leukaemic T cells, aberrant expression of class II MHC antigens on some B cell lymphomas and I-A-regulated chronic immunostimulation of MuLV-expressing (pre) leukaemic B cells, are discussed.
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PMID:The H-2 complex regulates both the susceptibility to mouse viral lymphomagenesis and the phenotype of the virus-induced lymphomas. 302 34

Neonatal infection of mice with Moloney murine leukemia virus (MuLV-M) results in the establishment of a chronic virus-carrier state. Such MuLV-carrier mice exhibit several immunologic abnormalities including generalized immunosuppression and autoimmunity. Previously, we found thymocytes from MuLV-M-carrier mice to be cytotoxic for normal syngeneic and allogeneic fibroblasts but not for xenogeneic (hamster) target cells. However, when the same syngeneic or allogeneic target cells were infected with MuLV-M, they were "spared" from the autoreactivity, leading us to speculate that the MuLV receptor on the target cell membrane was involved in the autoreactivity. To address this question, we tested MuLV-carrier thymocytes for their ability to lyse hamster/mouse-hybrid target cells; some of which possessed chromosome 5 (which codes for the ecotropic MuLV receptor). Of the nine hybrid cell lines initially tested, only the five clones that carried chromosome 5 were killed by the autoreactive thymocytes. In additional experiments, we noted that the cytotoxic reaction was inhibited in the presence of a monoclonal antibody that reacts with an MuLV-M gp70 epitope. The results suggest that the autoreactive cytotoxicity is mediated, at least in part, through the formation of a "bridge" between MuLV budding from the membrane of the thymocytes and the ecotropic MuLV receptor on the target cells.
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PMID:Immunologic mechanisms in the pathogenesis of virus-induced leukemia. IV. Mechanism of target cell recognition by autoreactive thymocytes. 387 12

Neonatal infection of C57BL and BALB/c mice by cloned ecotropic and dualtropic mink cell focus-inducing (MCF) murine leukemia viruses (MuLV) induces a wide spectrum of different lymphomas of T, B, and non-T/non-B cell types. Oncogenic dualtropic MCF viruses and poorly oncogenic ecotropic MuLV act synergistically in lymphomagenesis. Within one mouse strain virus-induced T-cell lymphomas arise earlier than B-cell lymphomas after neonatal inoculation of a single-cloned MuLV. The host genetic constitution, notably the H-2 complex has a marked influence on lymphoma type. This H-2 influence can be explained by an H-2-linked difference in penetration of the thymus early in life by oncogenic thymotropic MuLV, which in turn is correlated with, but not necessarily due to the magnitude of the anti-MuLV antibody response.
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PMID:Ecotropic and dualtropic mink cell focus-inducing murine leukemia viruses can induce a wide spectrum of H-2 controlled lymphoma types. 633 56

The Runx2 (Cbfa1, Pebp2alphaA, Aml3) gene was previously identified as a frequent target for transcriptional activation by proviral insertion in T-cell lymphomas of CD2-MYC transgenic mice. We have recently shown that over-expression of the full-length, most highly expressed Runx2 isoform in the thymus perturbs T-cell development, leads to development of spontaneous lymphomas at low frequency and is strongly synergistic with Myc. To gain further insight into the relationship of Runx2 to other lymphomagenic pathways, we tested the effect of combining the CD2-Runx2 transgene either with a Pim1 transgene (E(mu)-Pim1) or with the p53 null genotype, as each of these displays independent synergy with Myc. In both cases we observed synergistic tumour development. However, Runx2 appeared to have a dominant effect on the tumour phenotype in each case, with most tumours conforming to the CD3(+), CD8(+), CD4(+/-) phenotype seen in CD2-Runx2 mice. Neonatal infection of CD2-Runx2 mice with Moloney murine leukaemia virus (Moloney MLV) also led to a dramatic acceleration of tumour onset. Analysis of known Moloney MLV target genes in these lymphomas showed a high frequency of rearrangement at c-Myc or N-Myc (82%), and a significant number at Pim1 or Pim2 (23%), and at Pal1/Gfi1 (18%). These results indicate that Runx2 makes a distinct contribution to T-cell lymphoma development which does not coincide with any of the oncogene complementation groups previously identified by retroviral tagging.
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PMID:Runx2: a novel oncogenic effector revealed by in vivo complementation and retroviral tagging. 1131 58

In this study, we have exploited the power of insertional mutagenesis to elucidate tumor progression pathways in mice carrying two oncogenes (MYC/Runx2) that collaborate to drive early lymphoma development. Neonatal infection of these mice with Moloney murine leukemia virus resulted in accelerated tumor onset with associated increases in clonal complexity and lymphoid dissemination. Large-scale analysis of retroviral integration sites in these tumors revealed a profound bias towards a narrow range of target genes, including Jdp2 (Jundm2), D cyclin, and Pim family genes. Remarkably, direct PCR analysis of integration hotspots revealed that every progressing tumor consisted of multiple clones harboring hits at these loci, giving access to large numbers of independent insertion events and uncovering the contrasting mutagenic mechanisms operating at each target gene. Direct PCR analysis showed that high-frequency targeting occurs only in the tumor environment in vivo and is specific for the progression gene set. These results indicate that early lymphomas in MYC/Runx2 mice remain dependent on exogenous growth signals, and that progression can be achieved by constitutive activation of pathways converging on a cell cycle checkpoint that acts as the major rate-limiting step for lymphoma outgrowth.
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PMID:Insertional mutagenesis reveals progression genes and checkpoints in MYC/Runx2 lymphomas. 1754 90