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 expression of c-myb mRNA and protein was analyzed in fresh leukemic cells by Northern-blot analyses and by immunofluorescent staining using monoclonal c-myb specific antibodies. Staining of the cells was evaluated by flow cytometry. The results demonstrate c-myb mRNA expression predominantly in acute lymphocytic leukemia (ALL, 4/4 cases), acute myeloic leukemia (AML, 17/17) and chronic myeloic leukemia (CML, 12/12) but rarely in chronic lymphocytic leukemia (CLL, 1/17). Immunofluorescent analyses revealed expression of c-myb protein in the nucleus of ALL (5/7) and AML (9/9) with a good correlation of c-myb-positive cells and with the number of proliferating (Ki67-positive) blast cells.
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PMID:Heterogeneous expression of c-myb protein in human leukemia detected by simultaneous two color flow cytometric analysis. 156 Jun 75

The v-myb oncogene of the acute avian leukemia virus E26 encodes a transcription factor that directly regulates the promyelocyte-specific mim-1 gene (Ness, S.A., Marknell, A. and Graf, T. Cell, 59, 1115-1125). We have investigated the relationship between the c-myb proto-oncogene and the transcription of the mim-1 gene both in vitro and in vivo. We demonstrate that the c-myb protein can transactivate the transcription of mim-1 in a transient transfection assay. In the chick embryo, we confirm that mim-1 is specifically expressed during granulopoiesis and we show that the expression of c-myb and mim-1 are perfectly correlated in the granulocytic spleen and pancreas. However we suggest that mim-1 is efficiently transcribed in the absence of c-myb in the yolk sac and in the promyelocytes at the onset of the colonization of the bursa of Fabricius. On the other hand c-myb transcripts detected in the early hemopoietic progenitor cells, in lymphoid cells and in proliferative epithelia are never associated with mim-1 transcription. We conclude that the granulocyte-specific mim-1 gene is regulated by c-myb-dependent and c-myb-independent mechanisms depending upon the environment in which granulocytic precursor cells differentiate.
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PMID:Expression patterns of c-myb and of v-myb induced myeloid-1 (mim-1) gene during the development of the chick embryo. 157 54

We recently found that inhibition of MYB protein synthesis in human peripheral blood mononuclear cells (PBMC) exposed to human c-myb (designated MYB) antisense oligodeoxynucleotides prevents entry into S phase and cell proliferation. To determine the mechanism(s) by which down-regulation of human c-myb protein (MYB) synthesis interferes with DNA synthesis, we analyzed mRNA levels of DNA polymerase alpha and proliferating cell nuclear antigen (PCNA), transcripts of two genes required for DNA synthesis, in normal and leukemic T lymphocytes exposed to MYB antisense oligodeoxynucleotides. Expression of DNA polymerase alpha was inhibited both in normal T lymphocytes progressing from G0 to S phase and in exponentially growing CCRF-CEM leukemic cells, whereas expression of PCNA was inhibited only in mitogen-stimulated PBMC and remained essentially unaffected in the leukemia T-cell line. The functional link between expression of MYB and DNA polymerase alpha mRNAs was further demonstrated by analyzing DNA polymerase alpha mRNA levels in a temperature-sensitive (ts) fibroblast cell line (TK-ts13; TK is thymidine kinase) constitutively expressing human MYB mRNA driven by the simian virus 40 (SV40) promoter. In the MYB-expressing TK-ts13 cells, DNA polymerase alpha mRNA levels were unaffected following shift to the nonpermissive temperature of 39.6 degrees C, whereas in the parental line, DNA polymerase alpha mRNA levels were readily down-regulated. These findings indicate that the expression of MYB is related to that of DNA polymerase alpha in cells expressing MYB at high levels and suggest that there is a functional link between c-myb and DNA polymerase alpha mRNA expression during cell cycle progression of normal T lymphocytes.
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PMID:Inhibition of T-cell proliferation by a MYB antisense oligomer is accompanied by selective down-regulation of DNA polymerase alpha expression. 169 13

Two murine monocytic leukemia cell lines, WEHI-265 and WEHI-274, were found to carry a rearranged c-myb gene. The rearrangements are due to insertion of a deleted Moloney murine leukemia virus (Mo-MLV) provirus in the 5' region of the c-myb gene and thus are similar to rearrangements in the ABPL tumors (G. L. C. Shen-Ong, M. Potter, J. F. Mushinski, S. Lavu, and E. P. Reddy, Science 226:1077-1080, 1984). In each cell line, the retroviral insertion has induced high levels of two aberrant RNA species, which, as in the ABPL tumors (G. L. C. Shen-Ong, H. C. Morse, M. Potter, and J. F. Mushinski, Mol. Cell. Biol. 6:380-392, 1986), contain both viral (Mo-MLV) and cellular (myb) sequences. Both species lack the sequences encoding the amino terminus of the c-myb protein and thus could encode a protein which, like the v-myb gene products (and the predicted ABPL myb proteins), is truncated at the amino terminus. We have found that the larger (5.3 kilobase [kb]) and more abundant of the tumor-specific myb RNAs was predominantly nuclear, while the smaller species (3.9 kb) was cytoplasmic. Furthermore, our data imply that the 3.9-kb RNA was derived from the 5.3-kb RNA by an additional splice which utilized a cryptic splice acceptor site within the viral gag sequences. On the basis of subcellular distribution and predicted translational potential, we conclude that the 3.9-kb RNA is probably the mRNA which encodes a truncated myb protein. We also show that, due to different insertion points in W265 and W274, the W274 myb RNAs contained sequences from a c-myb exon upstream of the exons represented in the W265 (and ABPL) RNAs. The significance of our findings with regard to transformation by myb in these tumors is discussed.
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PMID:Generation of altered transcripts by retroviral insertion within the c-myb gene in two murine monocytic leukemias. 244 Oct 77

To study the role of the protooncogene c-myb in regulating myeloid leukemia cell proliferation and differentiation, we exposed cells of the human leukemia lines HL-60, ML-3, KG-1, and KG-1a to an oligodeoxynucleotide complementary to an 18-base-pair (bp) sequence of c-myb-encoded mRNA. This treatment resulted in a significant decrease in cell proliferation in all of the lines, which was most marked in HL-60 cells. After 5 days in culture, in several separate experiments with different oligomer preparations, 75% growth inhibition was observed in c-myb antisense treated cells in comparison to untreated HL-60 cells. Two c-myb antisense oligomers of identical length with either 2- or 4-bp mismatches had no effect on cell growth nor did an 18-bp c-myb sense or myeloperoxidase antisense oligomer. The effect of a c-myc antisense oligomer (18 bp) on the growth of HL-60, KG-1, and KG-1a cells was also studied. This oligomer had much less inhibitory effect on cell proliferation than did the c-myb antisense sequence. Interestingly, although c-myc antisense treatment induced maturation of HL-60 cells while it inhibited cell proliferation, such an effect was not noted in c-myb antisense treated cells. These studies indicate that the nuclear protein encoded by the c-myb protooncogene is required for maintenance of proliferation in certain leukemia cell lines. In compared to c-myc protein suggest that, at least in HL-60 cells, c-myc amplification or N-ras activation may not be sufficient to maintain the leukemic growth in the absence of c-myb protein. These findings support the hypothesis that development and maintenance of a malignant phenotype requires a multiplicity of interrelated genetic events.
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PMID:An oligomer complementary to c-myb-encoded mRNA inhibits proliferation of human myeloid leukemia cell lines. 254 45

To date, cellular transformation in vitro by the myb oncogene has been described for avian haemopoietic cells only. In order to exploit the well-characterized murine haemopoietic system to study transformation by myb, we have infected fetal liver cells with retroviral vectors carrying cDNAs that encode either complete or carboxy-terminally truncated c-myb proteins. We describe four cell lines which, despite our ability to efficiently infect haemopoietic target cells, were generated at low frequency. This was due, as least in part, to the requirement for a rearrangement within the vector that allowed expression of myb sequences. Three of the lines express a truncated myb protein while the fourth apparently expresses a normal c-myb protein, and thus constitutes an exception to the general association of truncation with transformation by myb. All four cell lines resemble immature cells of the myelomonocytic lineage and are dependent on colony-stimulating factors (CSFs) for their growth in vitro. One representative line could be converted to CSF-independence by infection with either Abelson murine leukaemia virus or a recombinant granulocyte-macrophage-CSF-encoding retrovirus; unlike the parental line, the resultant sublines were highly tumorigenic when injected into syngeneic mice.
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PMID:Murine myeloid cell lines derived by in vitro infection with recombinant c-myb retroviruses express myb from rearranged vector proviruses. 267 May 61

We have isolated cDNA clones of murine c-myb mRNA which contain approximately 2.8 kb of the 3.9-kb mRNA sequence. Nucleotide sequencing has shown that these clones extend both 5' and 3' to sequences homologous to the v-myb oncogenes of avian myeloblastosis virus and avian leukemia virus E26. The sequence contains an open reading frame of 1944 nucleotides, and could encode a protein which is both highly homologous, and of similar size (71 kd), to the chicken c-myb protein. Examination of the deduced amino acid sequence of the murine c-myb protein revealed the presence of a 3-fold tandem repeat of 52 residues near the N terminus of the protein, and has enabled prediction of some of the likely structural features of the protein. These include a high alpha-helix content, a basic region toward the N terminus of the protein and an overall globular configuration. The arrangement of genomic c-myb sequences, detected using the cDNA clones as probes, was compared with the reported structure of rearranged c-myb in certain tumour cells. This comparison suggested that the rearranged c-myb gene may encode a protein which, like the v-myb protein, lacks the N-terminal region of c-myb.
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PMID:Nucleotide sequence of cDNA clones of the murine myb proto-oncogene. 299 80

Two modes of disruption of the protooncogene c-myb by viral insertional mutagenesis in mouse myeloid tumor cells are described. The first mode was found in six tumors in which a Moloney murine leukemia virus component had inserted in the same transcriptional orientation upstream of the 5'-most exon with v-myb homology (vE1). cDNA sequence data indicate the presence of a truncated c-myb mRNA that is initiated in the upstream 5' long terminal repeat of the integrated provirus and processed via a cryptic splice donor sequence in the gag region to the splice acceptor site in vE1 of the c-myb gene, thus removing the remaining downstream viral and myb intronic sequences. Unlike most gag-onc transcripts, the gag and myb sequences in the hybrid transcript were not in the same reading frame. It is presumed that the gag sequence provides a cryptic translation initiation site for the novel amino-truncated c-myb protein. The second mode of disruption was by downstream virus insertion at the 3' side of the c-myb, which results in the synthesis of a small (approximately 2 kilobase) myb transcript. The 5' long terminal repeat of the inserted provirus provides a TGA termination codon that results in the elimination of 240 normal c-myb amino acid residues from the carboxyl terminus of the tumor-specific myb protein. These results suggest that truncated myb proteins play a role in neoplastic transformation of myeloid cells.
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PMID:Two modes of c-myb activation in virus-induced mouse myeloid tumors. 302 43

Avian myeloblastosis virus (AMV) is an oncogenic retrovirus that rapidly causes myeloblastic leukemia in chickens and transforms myeloid cells in culture. AMV carries an oncogene, v-myb, that is derived from a cellular gene, c-myb, found in the genomes of vertebrate species. We constructed a plasmid vector that allows expression of a portion of the coding region for v-myb in a procaryotic host. We then used the myb-encoded protein produced in bacteria to immunize rabbits. The antisera obtained permitted identification of the proteins encoded by both v-myb and chicken c-myb. The molecular weights of the products of v-myb and c-myb (45,000 and 75,000 respectively) indicate that the v-myb protein is an appreciably truncated version of the c-myb protein.
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PMID:The product of the retroviral transforming gene v-myb is a truncated version of the protein encoded by the cellular oncogene c-myb. 630 4

Proliferation of HL-60 and MOLT4 leukemia cells was inhibited by a c-myb antisense oligonucleotide (ASO) in the presence of a DNA uptake-stimulating protein (DNA uptake-stimulating factor, DUSF). The inhibitory effect was very mild in the absence of DUSF. Sense oligonucleotides or DUSF, alone or in combination, were found to be ineffective. Cellular expression of the c-myb protein was significantly more inhibited by the c-myb ASO in the presence than in the absence of DUSF. In the presence of DUSF, c-myb protein practically disappeared from the nuclei of HL-60 and MOLT4 cells treated with the ASO. Thus, DUSF appears to effectively stimulate the uptake of c-myb ASO into tumor cells in vitro, augmenting its antiproliferative effect by decreasing c-myb expression.
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PMID:A DNA uptake-stimulating protein increases the antiproliferative effect of c-myb antisense oligonucleotide on leukemic cells. 1556 4


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