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)

Insertional mutagenesis with Moloney murine leukemia virus (MoMLV) in c-myc and Pim-1 transgenic mice permits the identification of oncogenes that collaborate with the transgenes in lymphomagenesis. The recently identified common insertion site pal-1, in MoMLV-induced lymphomas, is located in a region in which several independent integration clusters are found: eis-1, gfi-1, and evi-5. Proviral insertions of MoMLV in the different integration clusters upregulate the transcriptional activity of the Gfi-1 gene, which is located within the pal-1 locus. The eis-1/pal-1/gfi-1/evi-5 locus serves as a target for MoMLV proviral insertions in pre-B-cell lymphomas of Emu-myc transgenic mice (20%) and in T-cell lymphomas of H-2K-myc (75%) and Emu-pim-1 (93%) transgenic mice. Many tumors overexpress both Gfi-1 as well as Myc and Pim gene family members, indicating that Gfi-1 collaborates with Myc and Pim in lymphomagenesis. Proviral integrations in the previously identified insertion site bmi-1 are, however, mutually exclusive with integrations in the eis-1/pal-1/gfi-1/evi-5 locus. This finding suggests that Bmi-1 and Gfi-1 belong to the same complementation group in lymphoid transformation.
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PMID:Characterization of pal-1, a common proviral insertion site in murine leukemia virus-induced lymphomas of c-myc and Pim-1 transgenic mice. 898 17

The bmi-1 gene was identified as a common proviral integration site in Moloney murine leukemia virus. In the present studies, we cloned and sequenced the rat bmi-1 gene by reverse transcriptase-polymerase chain reaction (RT-PCR) using degenerate PCR primers of homologous sequences between mouse and human. We found 93% identity to the mouse bmi-1 cDNA and 90% identity to the human bmi-1. The open reading frame encodes a protein of 324 amino acids. In the deduced amino acid sequence we observed 95% and 94% homology to the mouse and human, respectively. The structural motifs, a novel zinc finger motif and a putative helix-turn-helix motif, were conserved in the predicted rat BMI-1 protein. We also confirmed ubiquitous expression of bmi-1 in normal tissues except brain. These results suggest functional conservation of the bmi-1 gene in the rat.
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PMID:Cloning of the rat proto-oncogene bmi-1. 992 60

The bmi-1 gene was discovered as a clonal integration site of the Moloney murine leukaemia virus in B-cell lymphomas. The Bmi-1 protein contains the RING finger motif and is homologous to two Drosophila proteins known to be part of a multimeric protein complex involved in repressing gene transcription. A similar role for the highly conserved Bmi-1 protein in mammalian cells has been suggested. The coding regions for the mouse and human genes are known and are 92% homologous. This study involved PCR amplification, cloning, and sequencing of the 980bp feline bmi-1 coding region which was shown to be 92% and 97% homologous to the mouse and human genes respectively. From the open reading frame the feline protein is 326 amino acids in length and is 99% homologous to the human protein and 97% homologous to the mouse protein. This data is consistent with the closer relationship between the feline and human genomes and provides another experimental system in which to analyse Bmi-1 function.
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PMID:Nucleotide sequence of the feline Bmi-1 coding region. 1072 88

The MLL (mixed-lineage leukemia) gene is involved in many chromosomal translocations associated with acute myeloid and lymphoid leukemia. We previously identified a transcriptional repression domain in MLL, which contains a region with homology to DNA methyltransferase. In chromosomal translocations, the MLL repression domain is retained in the leukemogenic fusion protein and is required for transforming activity of MLL fusion proteins. We explored the mechanism of action of the MLL repression domain. Histone deacetylase 1 interacts with the MLL repression domain, partially mediating its activity; binding of Cyp33 to the adjacent MLL-PHD domain potentiates this binding. Because the MLL repression domain activity was only partially relieved with the histone deacetylase inhibitor trichostatin A, we explored other protein interactions with this domain. Polycomb group proteins HPC2 and BMI-1 and the corepressor C-terminal-binding protein also bind the MLL repression domain. Expression of exogenous BMI-1 potentiates MLL repression domain activity. Functional antagonism between Mll and Bmi-1 has been shown genetically in murine knockout models for Mll and Bmi-1. Our new data suggest a model whereby recruitment of BMI-1 to the MLL protein may be able to modulate its function. Furthermore, repression mediated by histone deacetylases and that mediated by polycomb group proteins may act either independently or together for MLL function in vivo.
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PMID:MLL repression domain interacts with histone deacetylases, the polycomb group proteins HPC2 and BMI-1, and the corepressor C-terminal-binding protein. 1282 90

Recent studies have suggested that one of the polycomb group genes, BMI-1, has an important role in the maintenance of normal and leukemic stem cells by repressing the INK4a/ARF locus. Here, we quantitatively examined BMI-1 expression level in samples from patients with acute myeloid leukemia (AML) and other hematologic malignancies. Moderate to high BMI-1 expression was detected in AML patients, and the BMI-1 expression levels in AML samples were significantly higher than in normal bone marrow controls (P = .0011). Specimens of French-American-British classification subtype M0 showed higher relative expression of the BMI-1 transcript (median, 390.2 3 10(-3)) than the other subtypes (median, 139.0 3 10(-3)) (P < .0001). Leukemia other than AML showed low to moderate expression. INK4a-ARF transcript expression tended to be inverse proportion to that of BMI-1. In an M0 patient with a high BMI-1 transcript level, the INK4a-ARF transcript level fell promptly and maintained a low value after the patient achieved complete remission. These results indicated that a subgroup of M0 patients has a high expression level of polycomb group gene BMI-1, which may contribute to leukemogenesis.
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PMID:BMI-1 is highly expressed in M0-subtype acute myeloid leukemia. 1610 58

Feline leukemia virus (FeLV), which is subclassified into three subgroups of A, B and C, is a pathogenic retrovirus in cats. FeLV-A is minimally pathogenic, FeLV-C can cause pure red cell aplasia, and FeLV-B is associated with a variety of pathogenic properties such as lymphoma, leukemia and anemia. FeLV-induced neoplasms are caused, at least in part, by somatically acquired insertional mutagenesis in which the integrated provirus may activate a proto-oncogene or disrupt a tumor suppressor gene. The common integration sites for FeLV have been identified in six loci with feline lymphomas: c-myc, flvi-1, flvi-2 (contains bmi-1), fit-1, pim-1 and flit-1. Oncogenic association of the loci includes that c-myc is known as a proto-oncogene, bmi-1 and pim-1 have been recognized as myc-collaborators, fit-1 appears to be closely linked to myb, and flit-1 insertion is shown to be associated with over-expression of a cellular gene, e.g. ACVRL1. Thus, identification of common integration sites for FeLV is a tenable model to clarify oncogenesis. Recent advances in molecular biology and cytogenetics have developed to rapidly detect numbers of retroviral integration sites by genome-wide large-scale analyses. Especially, polymerase chain reaction (PCR)-based strategies and chromosome analyses with fluorescence in situ hybridization (FISH) will be applicable for studies on FeLV.
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PMID:Molecular pathogenesis of feline leukemia virus-induced malignancies: insertional mutagenesis. 1831 64

Deregulated HOX expression, by chromosomal translocations and myeloid-lymphoid leukemia (MLL) rearrangements, is causal in some types of leukemia. Using real-time reverse transcription-PCR, we examined the expression of 43 clustered HOX, polycomb, MLL and FLT3 genes in 119 newly diagnosed adult acute myeloid leukemias (AMLs) selected from all major cytogenetic groups. Downregulated HOX expression was a consistent feature of favorable AMLs and, among these cases, inv(16) cases had a distinct expression profile. Using a 17-gene predictor in 44 additional samples, we observed a 94.7% specificity for classifying favorable vs intermediate/unfavorable cytogenetic groups. Among other AMLs, HOX overexpression was associated with nucleophosmin (NPM) mutations and we also identified a phenotypically similar subset with wt-NPM. In many unfavorable and other intermediate cytogenetic AMLs, HOX levels resembled those in normal CD34+ cells, except that the homogeneity characteristic of normal samples was not present. We also observed that HOXA9 levels were significantly inversely correlated with survival and that BMI-1 was overexpressed in cases with 11q23 rearrangements, suggesting that p19(ARF) suppression may be involved in MLL-associated leukemia. These results underscore the close relationship between HOX expression patterns and certain forms of AML and emphasize the need to determine whether these differences play a role in the disease process.
Leukemia 2008 Nov
PMID:HOX expression patterns identify a common signature for favorable AML. 1866 34

BMI-1 (B-cell-specific Moloney murine leukemia virus integration site 1), a novel oncogene, has attracted much attention in recent years for its involvement in the initiation of a variety of tumors. Recent evidence showed that BMI-1 was highly expressed in neoplastic skin lesions. However, whether dysregulated BMI-1 expression is causal for the transformation of skin cells remains unknown. In this study, we stably expressed BMI-1 in a human keratinocyte cell line, HaCaT. The expression of wild-type BMI-1 induced the malignant transformation of HaCaT cells in vitro. More importantly, we found that expression of BMI-1 promoted formation of squamous cell carcinomas in vivo. Furthermore, we showed that BMI-1 expression led to the downregulation of tumor suppressors, such as p16INK4a and p14ARF, cell adhesion molecules, such as E-Cadherin, and differentiation related factor, such as KRT6. Therefore, our findings demonstrated that dysregulated BMI-1 could indeed lead to keratinocytes transformation and tumorigenesis, potentially through promoting cell cycle progression and increasing cell mobility.
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PMID:Oncoprotein BMI-1 induces the malignant transformation of HaCaT cells. 1902 Nov 48

This study was aimed to investigate the expression of SALL4 and BMI-1 mRNA in acute leukemia (AL) and its clinical significance. mRNA expression levels of SALL4 and BMI-1 in 62 AL patients and 10 controls were measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). The results showed that (1) the expression of SALL4 mRNA were up-regulated in AL (except M3 and T-ALL), and the expression of of SALL4 mRNA in AML was significantly higher than that in B-ALL (p<0.05); expression was negative in 9 out of 10 controls, and expression level of SALL4 mRNA in one case was low; (2) the expression of SALL4 in de novo AL was higher than that in controls, which significantly decreased at complete remission (CR). The difference between CR group and de novo group was statistically significant (p<0.05). In relapsed patients, the expression of SALL4 increased, slightly higher than that in de novo AL group (p>0.05); (3) the expression pattern of BMI-1 was the same to that of SALL4 except the up-regulation in M3, and the expression of BMI-1 was positively correlated with that of SALL4 in acute leukemia (r=0.684, p<0.01). It is concluded that SALL4 and BMI-1 expressions are up-regulated significantly in acute leukemia, which may contribute to the development of leukemia, thus become an important index for evaluation of development, relapse and prognosis in acute leukemia.
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PMID:[Expression of SALL4 and BMI-1 mRNA in acute leukemia]. 1909 25

Polycomb protein BMI-1 is often overexpressed in various types of leukemia, and its depletion in those leukemic cells leads to cell proliferation arrest, differentiation, and apoptosis. These findings have led us to believe that Bmi-1 has potential as a therapeutic target for leukemia. In this study, we tested multiple sets of synthetic siRNA oligo pairs for downregulating the expression of Bmi-1 in U937 cells, and explored the possible biological effects of BMI-1 suppression on cell growth and proliferation. We found that one siRNA oligo pair can efficiently knock down BMI-1 in U937 cells as evaluated by real-time RT-PCR as well as Western blot analysis. Furthermore, we found that BMI-1 depletion leads to reduced cell growth and proliferation, and increased cell apoptosis. Our proof-of-principle findings confirm that Bmi-1 siRNA can be used as a therapeutic target of any Bmi-1 expressing leukemia and other cancer cells.
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PMID:Anti-proliferation effect of BMI-1 in U937 cells with siRNA. 2223 89


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