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)

An expression sequence tag identified in a screen for genes upregulated by retinoic acid induced neuronal differentiation of the human teratocarcinoma cell line Ntera2/D1 was found in close genomic proximity to a region of high sequence homology to the septin subfamily of GTPase genes. We could show that the tag corresponds to the 3' untranslated region of this novel gene named septin 3 and cloned three isoforms A (2191 bp), B (4378 bp), and C (1896 bp) from human Ntera2/D1 cDNA. We present the genomic localization and organization on chromosome 22q13.2, a chromosomal hot spot for translocations implicated in leukemia. Interestingly, MSF the closest paralog of septin 3 is a fusion partner in a therapy-related acute myeloid leukemia. Quantitative PCR confirmed the upregulation of the putative septin by neuronal differentiation and northern blotting showed only one band corresponding to sep3B with a neurospecific expression pattern in adult human tissues.
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PMID:Human septin 3 on chromosome 22q13.2 is upregulated by neuronal differentiation. 1132 66

In attempting to develop effective anticancer immunotherapies, the relative ability of apoptotic cells to induce an immune response remains an important but controversial consideration. A novel gene-transfer approach was used by which rapid induction of pure apoptosis can be selectively achieved in a transfected tumor cell population following exposure to a semisynthetic dimerizing ligand, AP20187. Inoculation of BALB/c mice with apoptotic and viable 12B1-D1 leukemia cells, at a 12:1 ratio subcutaneously, led to early tumor growth. Heat stress up-regulated the expression of membrane heat shock proteins (HSP72 and HSP60) on apoptotic 12B1-D1 cells, and stressed apoptotic cells were capable of generating a T-cell-mediated specific antitumor response. Pulsing of stressed apoptotic leukemia cells onto syngeneic dendritic cells resulted largely in rejection of coinjected viable 12B1-D1 cells. Mice rejecting the primary 12B1-D1 inoculum were immune to the same but not to a different leukemia challenge. Our findings indicate that tumor immunogenicity is dependent on whether cells are stressed before apoptosis induction and suggest that the immune system is capable of distinguishing between stressed and nonstressed cells undergoing programmed cell death. (Blood. 2001;97:3505-3512)
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PMID:Stressed apoptotic tumor cells express heat shock proteins and elicit tumor-specific immunity. 1136 44

Using differential display-polymerase chain reaction, we identified a novel gene sequence, designated solid tumor-associated gene 1 (STAG1), that is upregulated in renal cell carcinoma (RCC). The full-length cDNA (4839 bp) encompassed the recently reported androgen-regulated prostatic cDNA PMEPA1, and so we refer to this gene as STAG1/PMEPA1. Two STAG1/PMEPA1 mRNA transcripts of approximately 2.7 and 5 kb, with identical coding regions but variant 3' untranslated regions, were predominantly expressed in normal prostate tissue and at lower levels in the ovary. The expression of this gene was upregulated in 87% of RCC samples and also was upregulated in stomach and rectal adenocarcinomas. In contrast, STAG1/PMEPA1 expression was barely detectable in leukemia and lymphoma samples. Analysis of expressed sequence tag databases showed that STAG1/PMEPA1 also was expressed in pancreatic, endometrial, and prostatic adenocarcinomas. The STAG1/PMEPA1 cDNA encodes a 287-amino-acid protein containing a putative transmembrane domain and motifs that suggest that it may bind src homology 3- and tryptophan tryptophan domain-containing proteins. This protein shows 67% identity to the protein encoded by the chromosome 18 open reading frame 1 gene. Translation of STAG1/PMEPA1 mRNA in vitro showed two products of 36 and 39 kDa, respectively, suggesting that translation may initiate at more than one site. Comparison to genomic clones showed that STAG1/PMEPA1 was located on chromosome 20q13 between microsatellite markers D20S183 and D20S173 and spanned four exons and three introns. The upregulation of this gene in several solid tumors indicated that it may play an important role in tumorigenesis.
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PMID:Characterization of a novel gene, STAG1/PMEPA1, upregulated in renal cell carcinoma and other solid tumors. 1156 75

Both AIDS and cancer are linked to immune dysfunctions of the body which are characterized by the persistence of disease-afflicted cells. To effect a cure with novel gene therapy approaches, these diseased cells must be eliminated either directly or indirectly using cytotoxic or suicide genes, or via activation of specific immune functional cells. Retroviral vectors are useful tools for long-term genome modification owing to their ability to integrate into host chromosomes. However, most oncoretroviruses, including murine leukemia virus (MLV), require cell division to facilitate nuclear entry; this has restricted the application of murine oncoretroviral vectors to cell targets that are actively dividing. Accordingly, gene transfer into hematopoietic stem cells (HSCs) and terminally differentiated cells such as muscles, neurons and dendritic cells (DCs) has been limited with the conventional oncoretroviral vectors. The lentiviral family of retroviruses, including human immunodeficiency virus type 1 (HIV-1), has been developed into useful gene transfer tools. Lentiviral vectors carry several nuclear entry viral proteins, and therefore can target slowly-dividing and non-dividing cells. To activate immune response against cancer or HIV infection, long-term marking of the target cells is not necessary. However, to establish intracellular defense to prevent HIV infection, prolonged genetic modification of target cells such as HSCs will be required. Due to the poor transduction efficiency and the problem of transgene silencing over time with oncoretroviral vectors, most gene therapy studies for AIDS and cancer using oncoretroviral vectors remain proof-of-concept studies. Here we will discuss recent developments in the use of retroviral vectors, including HIV-1-derived lentiviral vectors, for the treatment of AIDS and cancer, and their future therapeutic potential.
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PMID:Retroviral vectors for gene therapy of AIDS and cancer. 1169 91

We encountered a patient with Philadelphia-negative chronic myeloid leukaemia, with t(7;11)(p15;p15), in whom acute leukaemia phase (acute myeloid leukaemia-M2 morphology) developed within a short period. We detected a novel gene fusion between NUP98 and HOXA11 both in the chronic phase and in the acute leukaemia phase in this case. Although it is well known that a fusion of NUP98-HOXA9 in myeloid malignancies is created by the t(7;11)(p15;p15), this case suggests the possibility that HOXA11 might be another partner gene for NUP98 in t(7;11)(p15;p15) leukaemia.
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PMID:t(7;11)(p15;p15) Chronic myeloid leukaemia developed into blastic transformation showing a novel NUP98/HOXA11 fusion. 1184 13

In this paper we sought to analyze the genomic structure and context of human feline leukemia virus subgroup C receptor (hFLVCR), a human glucarate transporter-like gene at chromosome 1q31, and compare it to that of a paralog (FLVCR14q) at chromosome 14q24. Splicing, polyadenylation, and expression patterns, as estimated by in silico analysis, differed between the two FLVCR genes despite their similar genomic structures, suggesting active and independent evolution of transcriptional and messenger RNA processing patterns after gene duplication. Promoter activity was bi-directional for hFLVCR, but not for its 14q paralog. The upstream 1q transcribed sequences were determined to comprise a novel gene of unknown function, LQK1. Annotation of contigs centered at hFLVCR and FLVCRL14q also revealed highly conserved gene clusters on chromosomes 1 and 14, inferred to result from a duplication. The clusters contained members of the FLVCR, Angel (KIAA0759), JDP, p21SNFT, and TGF- families, as well as two uncharacterized families. The genome-wide locations of both previously recognized and four de novo in silico predicted genes belonging to these seven families were determined. Phylogenetic analyses of these families were consistent with the hypothesis that the 1q/14q duplication occurred early within, or immediately prior to the vertebrate divergence, after the protostome-deuterostome divergence but before the amniote-amphibian divergence.
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PMID:Genomic structure and evolutionary context of the human feline leukemia virus subgroup C receptor (hFLVCR) gene: evidence for block duplications and de novo gene formation within duplicons of the hFLVCR locus. 1194 75

Chromosome band 6q21 is reported to be one of the most frequent target regions in T-cell lymphoma for both translocations and deletions. To explore whether the breakpoint clustering in T-cell malignancy indicates the presence of a common breakpoint region in 6q, we employed fluorescence in situ hybridization analysis using various YAC, BAC, and PAC clones aligned at 6q21-22. We identified two T-cell lymphoma/leukemia cell lines with different differentiation stages that had breakpoints within the same novel gene, TCBA1 (T-cell lymphoma breakpoint associated target 1). In a T-cell lymphoblastic lymphoma cell line, HT-1, the TCBA1 fused to SUSP1 (SUMO-1-specific protease), creating a SUSP1-TCBA1 chimeric gene. However, in an adult T-cell leukemia cell line, ATN-1, no chimeric gene was detected, although aberrant TCBA1 transcripts were produced. We conclude that TCBA1 is a possible target gene for T-cell lineage-specific chromosome aberrations at 6q21.
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PMID:Molecular cytogenetic analysis of the breakpoint region at 6q21-22 in T-cell lymphoma/leukemia cell lines. 1197 51

Tumor necrosis factor (TNF) is a multifunctional cytokine, which induces proliferation or death in a cell type-dependent manner. We previously showed that murine embryonic fibroblasts (MEFs) from TNF receptor-associated factor 2 (Traf2) and Traf5 double-deficient (double knockout (DKO)) mice were highly susceptible to TNF-induced cell death. By functional cloning to rescue DKO MEFs from TNF-induced cell death, we have identified a novel gene, Bsac. BSAC is composed of N-terminal basic, SAP (SAF-A/B, Acinus, PIAS), and coiled-coil domains. BSAC is a nuclear protein, and overexpression of BSAC potently activates promoters containing A + T-rich sequences named CArG boxes. Domain mapping analysis revealed that both N-terminal basic and C-terminal proline-rich sequence are required for the transcriptional activity. Overexpression of BSAC in DKO MEFs partially inhibited TNF-induced cell death by suppressing activation of caspases. Interestingly, inhibition of TNF-induced cell death was not observed in DKO MEFs transfected with either N-terminal or C-terminal deletion mutant of BSAC, revealing an intimate correlation between transcriptional activity and antiapoptotic function. Recently, a human homologue of BSAC named MAL/MKL1 (megakaryocytic acute leukemia/megakaryoblastic leukemia-1) was identified as a fusion transcript generated by t(1,22) translocation in acute megakaryoblastic leukemia. Collectively, BSAC is a novel transcriptional activator with antiapoptotic function, which may be involved in the leukemogenesis.
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PMID:Identification of a novel transcriptional activator, BSAC, by a functional cloning to inhibit tumor necrosis factor-induced cell death. 1201 65

A novel gene, named embryonic develop associated gene 1 ( EDAG -1) and abundantly expressed in human fetal liver tissues, was isolated by screening a human fetal liver cDNA library and the 5' RACE. The full length of EDAG-1 mRNA is 2 166 bp, with an open reading frame of 1 452 bp neucleotides, encoding a 484 amino acid protein. No domain or motif was found similar with other genes by Blast program. Two copies of AUUUA motif in 3' non-translated region show instability of its mRNA. The molecular weight of the protein is 55.3 kD identified by the translation in vitro. EDAG-1 is specifically expressed in hematopoietic tissues, and is quickly down-regulated during the differentiation of K562 cells induced by hemin and EPO. These results show that EDAG-1 is related to the regulation in hematopoietic system and the development of leukemia.
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PMID:Isolation and Characterization of EDAG-1, A Novel Gene Related to Regulation in Hematopoietic System. 1203 55

The Ahi-1 locus was initially identified as a common helper provirus integration site in Abelson pre-B-cell lymphomas and shown to be closely linked to the c-myb proto-oncogene. Since no significant alteration of c-myb expression was found in Abelson murine leukemia virus-induced pre-B-lymphomas harboring a provirus inserted within the Ahi-1 locus, this suggested that it harbors another gene whose dysregulation is involved in tumor formation. Here we report the identification of a novel gene (Ahi-1) targeted by these provirus insertional mutations and the cloning of its cDNA. The Ahi-1 proviral insertions were found at the 3' end of the gene, in an inverse transcriptional orientation, with most of them located around and downstream of the last exon, whereas another insertion was within intron 22. In addition, another previously identified provirus insertion site, Mis-2, was found to map within the 16th intron of the Ahi-1 gene. The Ahi-1 cDNA encodes a 1,047-amino-acid protein. The predicted Ahi-1 protein is a modular protein that contains one SH3 motif and seven WD40 repeats. The Ahi-1 gene is conserved in mammals and encodes two major RNA species of 5 and 4.2 kb and several other shorter splicing variants. The Ahi-1 gene is expressed in mouse embryos and in several organs of the mouse and rat, notably at high levels in the brain and testes. In tumor cells harboring insertional mutations in Ahi-1, truncated Ahi-1/viral fused transcripts were identified, including some splicing variants with deletion of the SH3 domain. Therefore, Ahi-1 is a novel gene targeted by provirus insertion and encoding a protein that exhibits several features of a signaling molecule. Thus, Ahi-1 may play an important role in signal transduction in normal cells and may be involved in tumor development, possibly in cooperation with other oncogenes (such as v-abl and c-myc) or with a tumor suppressor gene (Nf1), since Ahi-1 insertion sites were identified in tumors harboring v-abl defective retroviruses or a c-myc transgene or in tumors exhibiting deletion of Nf1.
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PMID:Ahi-1, a novel gene encoding a modular protein with WD40-repeat and SH3 domains, is targeted by the Ahi-1 and Mis-2 provirus integrations. 1218 88


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