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)

The c-myc and N-myc nuclear oncoproteins are implicated in the genesis and maintenance of the transformed phenotype in several types of neoplastic disease, and the c-myc protein is involved in the progression of normal cells through the cell cycle. We have designed and developed sensitive and quantitative ELISAs for these proteins. Myc proteins are captured from cell lysates by an antibody directed against a peptide sequence substantially conserved in all known myc proteins; the captured proteins are recognised by a specific anti-c-myc or anti-N-myc monoclonal antibody conjugated to alkaline phosphatase; bound alkaline phosphatase is measured with an extremely sensitive cycling enzyme system that generates a coloured end-product. The c-myc assay is calibrated using bacterially expressed human c-myc protein. We have used this assay to estimate the number of c-myc molecules in a range of normal and transformed cells of human, murine, and feline origin; to monitor increases in c-myc expression when quiescent cells are stimulated with growth factors; and to follow the decrease in c-myc protein levels when HL60 promyelocytic leukaemia cells are induced to differentiate with dimethylsulphoxide or phorbol esters.
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PMID:A sensitive and quantitative enzyme-linked immunosorbence assay for the c-myc and N-myc oncoproteins. 333 75

The cell line AG-F was isolated from the marrow of a neuroblastoma patient undergoing myeloablative treatment and autologous bone marrow rescue. A year later, the patient developed a Hodgkin's type lymphoma. AG-F cell line demonstrated an unusual phenotype, lacking surface CD2 and CD3, but expressing high levels of CD4, CD5, CD7, CD29, and CD45RO. Markers associated with Hodgkin's lymphoma cells, CD15 and CD30, were also positive. AG-F cells grow in suspension in clusters of 50-200 cells, with a doubling time of 9 h. They can also grow in serum-free medium and form tumors in nude mice. AG-F cells have amplified N-myc and c-myc and high levels of the corresponding mRNA transcripts. Cytogenetic analysis revealed a DNA index by flow cytometry of near tetraploid cells and a karyotype of 85-87 chromosomes, with consistent abnormalities in chromosomes 1, 5, and 9. Gene rearrangement studies revealed rearrangement of the beta gene of the T-cell receptor. AG-F cells secrete high levels of IL-6, IL-8, IL-10, and GM-CSF. Cell adherence and formation of long processes could be induced by fibronectin and were enhanced by exposure to PMA. Cells exposed to phorbol myristate acetate (PMA) had increased expression of CD11a, CD11b, CD18, CD45RO, and HLA-DR, whereas expression of CD15 and CD30 was markedly decreased. Similarly, the level of c-myc and N-myc oncoproteins and the levels of the cytoskeletal proteins, actin, tubulin, and vimentin markedly decreased early after PMA-induced differentiation.
Leukemia 1993 Dec
PMID:Isolation and characterization of an early T-helper/inducer cell line with a unique pattern of surface phenotype, constitutive cytokine secretion and myc oncogene expression. 825 4

The myc proto-oncogenes encode nuclear DNA-binding phosphoproteins which regulate cell proliferation and differentiation. The c-myc gene is implicated in hematopoietic malignancies on the basis of its frequent deregulation in naturally occurring leukemias and lymphomas. Recent evidence suggests that also the N-myc and L-myc genes may have a role in normal and malignant hematopoiesis. N-myc and to a certain degree L-myc can substitute for c-myc in transformation assays in vitro, and their overexpression can block the differentiation of leukemia cell lines. Immunoglobulin heavy chain enhancer (IgH) -driven overexpression of N-myc or L-myc genes cause lymphatic and myeloid tumors, respectively, in transgenic mice. Furthermore, the L-myc and N-myc genes are expressed in several human leukemias and leukemia cell lines, L-myc predominantly in myeloid and N-myc both in myeloid and in some lymphoid leukemias. All N/L-myc positive leukemias and leukemia cell lines coexpress the c-myc gene, thus exemplifying a lack of negative cross-regulation between the different myc genes in leukemia cells. Taken together, these data suggest that L-myc and N-myc may participate in the growth regulation of hematopoietic cells.
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PMID:L-myc and N-myc in hematopoietic malignancies. 826 Aug 94

Rearrangements of the N-myc oncogene have not been described in the literature. The authors present a case of ANLL with the N-myc gene rearranged out of 16 ANLLs and 11 ALLs. While the proportion of the blast cells in the case reported was 85%, the rearranged gene gave a hybridization band which was less intense than that of the germline band, making it probable that this gene rearrangement is present in a leukemia subclone. The c-myc oncogene as well as Ig and TcR genes were in germline configurations. The presence of the rearranged N-myc in the reported case could imply an alternative mechanism of mutation of this oncogene in the pathogenesis of hematological malignancies.
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PMID:Rearrangement of the N-myc oncogene in acute leukemias: a case report. 835 17

Although the v-abl gene can provoke several types of lymphoid neoplasm, mice of a transgenic strain (E mu-v-abl 40) in which lymphocytes are targeted for expression of v-abl by a linked immunoglobulin enhancer (E mu) spontaneously develop only plasmacytomas. To determine whether other lymphocytes of this strain were susceptible to transformation, and to identify genes that can collaborate with v-abl in tumorigenesis, E mu-v-abl 40 mice were subjected to insertional mutagenesis by neonatal infection with Moloney murine leukemia virus. Tumorigenesis was accelerated moderately, but nearly all the tumors were T lymphomas. The altered tumor type may reflect both the T-cell tropism of Moloney virus and the higher level of E mu-v-abl 40 expression found in T lymphocytes than in B lymphocytes. Insertion near the c-myc, N-myc or pim-I gene was observed in 42% of the induced tumors, indicating that each of these genes may collaborate with v-abl in lymphomagenesis. Most of the accelerated tumors had a surprisingly low level of transgene expression. Thus, high expression of v-abl may not be required for Moloney-induced T lymphomagenesis.
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PMID:Moloney virus induction of T-cell lymphomas in a plasmacytomagenic strain of E mu-v-abl transgenic mice. 840 91

Intrathymic injection of Moloney murine leukemia virus (Mo-MuLV)-pseudotyped bcr-abl retrovirus (bcr-abl/M) causes thymic lymphoma but only after a prolonged latent period similar to that seen after intrathymic injection of Mo-MuLV alone. Since thymomas induced by Mo-MuLV show recurring proviral integration near certain cellular proto-oncogenes, it was reasoned that if the pathogenesis of bcr-abl/M thymomas is affected by viral integration, then it may be possible to detect proviral insertion near common Mo-MuLV integration sites in bcr-abl-induced thymomas. A panel of thymomas induced by intrathymic injection of Mo-MuLV, Abelson murine leukemia virus (A-MuLV), or the bcr-abl/M virus was analyzed for proviral integration near c-myc, N-myc, Pim-1, and Mlvi-1 loci that are frequently occupied by provirus in Mo-MuLV-induced T cell lymphomas, and for integration near Ahi-1 that is often occupied in A-MuLV/M-induced pre-B cell lymphoma. As expected, thymomas induced with Mo-MuLV showed frequent rearrangements in these loci while thymomas induced with A-MuLV/M (which does not require Mo-MuLV) did not. The bcr-abl/M-induced tumors also showed recurring proviral integration near c-myc, Pim-1 and Mlvi-1, albeit at a lower frequency than seen in the Mo-MuLV tumors. Unexpectedly, four independent thymomas that were clearly of T cell origin demonstrated proviral integration within the Ahi-1 region which was previously thought to only occur in A-MuLV/M induced pre-B cell lymphoma. These observations suggest that recurring proviral insertion in c-myc, Pim-1, Mlvi-1, and Ahi-1 may provide a selective advantage for bcr-abl/M transformed T lymphoid cells. This model may provide a tool for identifying cellular genes that can cooperate with bcr-abl in lymphoid transformation.
Leukemia 1997 Jul
PMID:Recurring proviral integration suggests a role for proto-oncogene activation in thymomas induced with Mo-MuLV-rescued BCR/ABL virus. 920 86

To investigate the regulatory mechanism of the expression of the multidrug resistance gene (mdr-1) and the multidrug resistance-associated protein gene (mrp), we investigated if p53, WT1, RB, C-myc, N-myc, cyclin D1, p16INK4 (p16) are involved in the acquirement of multidrug resistance phenotype (MDR) in human vincristine (VCR)-resistant cells of leukemia/lymphoma cell lines. By using RT-PCR, we observed that MDR in VCR-resistant cell lines was mediated by either mdr-1 or mrp genes. In cells that acquired the overexpression of mdr-1, downregulation of p53 and upregulation of WT-1 were observed. In contrast, no constant change of genes was observed in cells that overexpressed mrp. Although the change in the expression level of cyclin D1 and p-16 accompanied the development of VCR resistance, the mRNA of RB, C-myc and N-myc showed no correlation with the degree of VCR resistance or the level of mdr-1 expression. These results may provide a plausible diagnostic marker for determination of drug sensitivity in cancer patients and suggest that p53 may mediate directly or indirectly the expression of mdr-1 via WT1 in VCR-resistant hematologic cell lines.
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PMID:p53 may mediate the mdr-1 expression via the WT1 gene in human vincristine-resistant leukemia/lymphoma cell lines. 971 58

Little is known about stepwise deregulation of specific genes leading to lymphoid malignancy. Aberrant myc gene expression in transgenic mice is correlated with B cell lymphomagenesis. We generated a unique transgenic mouse model in which deregulated murine E mu-N-myc transgene expression leads to development of indolent B cell lymphoma. Tumor cells were monoclonal, morphologically mature and surface immunoglobulin expressing B cells. Tumors arose in a disease course and exhibited a cytoarchitectural appearance reminiscent of human follicular lymphoma. Yet tumor cells were staged as preB since they failed to rearrange the immunoglobulin light chain genes. Retroviral insertion mutagenesis analyses of adult transgenic mice infected as newborns with murine leukemia virus revealed decreased disease latency, increased lymphoma incidence and a histologically more mature tumor type. Proviral insertion sites were not equivalent when accelerated E mu-N-myc indolent lymphomas were compared to accelerated c-myc preB cell lymphomas. The bcl-2 gene was not disrupted in either spontaneous or provirally accelerated E mu-N-myc lymphomas. These findings suggest that tumor progression in N-myc-associated indolent B cell lymphoma can proceed along diverse pathways involving distinctly different combinations of deregulated and/or intact genes than those pathways described in highly aggressive forms of myc-related murine preB cell disease.
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PMID:Transgenic N-myc mouse model for indolent B cell lymphoma: tumor characterization and analysis of genetic alterations in spontaneous and retrovirally accelerated tumors. 979 78

The v-Myb oncogene causes late onset T cell lymphomas when expressed in the T cell lineage of transgenic mice. In order to define the cellular mutations cooperating with s-Myb to cause lymphomas, we have infected v-Myb transgenic mice with Moloney murine leukemia virus (M-MuLV). Tumor formation is significantly accelerated from a mean age of onset of 60 weeks in uninfected vMyb transgenics to 13 weeks in infected vMyb transgenics. We studied the loci into which the M-MuLV had inserted, and found that in 73% of animals, either the c-myc or the N-myc genes had been disrupted and deregulated. Therefore, v-myb and c-myb can cooperate to induce T cell lymphomas.
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PMID:Cooperation of Myb and Myc proteins in T cell lymphomagenesis. 1038 Aug 86

The chimeric transcription factor E2a-Pbx1 is expressed as a result of the 1;19 chromosomal translocation in some 5% of cases of pediatric acute lymphoblastic leukemia. We investigated the biological and transcriptional consequences of forced expression of E2a-Pbx1 in the interleukin-3 (IL-3) dependent, bone marrow-derived cell line Ba/F3. We show that forced expression of E2a-Pbx1 induces apoptosis in Ba/F3 cells without apparent effects on cell cycle progression. This pro-apoptotic effect is enhanced on cytokine deprivation. Furthermore, using cDNA representational difference analysis (RDA), we show that these cellular effects are associated with marked induction of the gene NDRG1, which was previously identified as a target of transcriptional repression by N-myc and induction by the tumor suppressor protein p53. We identify a portion of the NDRG1 promoter capable of mediating transcriptional induction by E2a-Pbx1 and show that NDRG1 is also induced on simple IL-3 deprivation of BaF3 cells. Although we show that E2a-Pbx1 induction of NDRG1 is not impaired as a result of targeting p53 using HPV E6, and therefore does not appear to be p53-dependent, our results overall are consistent with the notion that induction of NDRG1 by E2a-Pbx1 may represent part of an apoptotic or cytostatic cellular response to oncogene activation.
Leukemia 2001 Mar
PMID:The leukemogenic transcription factor E2a-Pbx1 induces expression of the putative N-myc and p53 target gene NDRG1 in Ba/F3 cells. 1123 58


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