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 rhombotin (RBTN1 or Ttg-1) gene was first identified at a chromosome translocation in a T-cell acute leukaemia and later used to isolate two related genes (RBTN2 or Ttg-2 and RBTN3). Complete characterization of these genes in man and mouse shows that all three encode cysteine-rich proteins with typical LIM domains. RBTN1 and RBTN3-derived proteins have 98% identity in the LIM domains but are located on separate chromosomes in man and in mouse while RBTN1 and RBTN2, both located on human chromosome 11p but are on separate chromosomes in mouse, are only 48% identical in this part of the protein. The exon organization of RBTN1 and RBTN3 genes are similar, both having an intron, absent from the RBTN2 gene, in the LIM2-encoding region. The remarkable similarity between rbtn-1 and rbtn-3 proteins is parallelled in their expression patterns in mouse development, since both genes show high expression in restricted areas of the brain, but little lymphoid expression. rbtn-2 expression, however, is more ubiquitous. This gene shows a low level of thymus expression but high expression in fetal liver, adult spleen and B-cell lines, consistent with a role in B-cell development. These results suggest multiple cellular targets for the action of these proteins during development.
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PMID:The rhombotin gene family encode related LIM-domain proteins whose differing expression suggests multiple roles in mouse development. 150 24

T-cell translocation gene 1 (Ttg-1), also called rhombotin, is deregulated upon translocation into the alpha/delta T-cell receptor loci in acute lymphoblastic leukemias bearing the t(11;14)(p15;q11). Ttg-1 encodes a nuclear protein, expressed predominantly in neuronal cells, which belongs to a novel family of transcription factors possessing LIM domains. We utilized the lck proximal promoter to overexpress this candidate oncogene in immature thymocytes of transgenic mice. lckPr Ttg-1 mice develop immature, aggressive T-cell leukemia/lymphomas. Tumor incidence is proportional to the level of Ttg-1 expression. Most tumors contain CD4+8+ cells as well as CD4-8+ cells, which have an immature rather than a mature peripheral phenotype. Ttg-1-induced tumorigenesis preferentially affects a minority population of thymocytes representing an immature CD4-8+ intermediate stage between double-negative CD4-8- cells and double-positive CD4+8+ cells. This model indicates that the aberrant expression of putative transcription factors plays a primary role in the genesis of T-cell acute lymphoblastic leukemias.
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PMID:Thymic overexpression of Ttg-1 in transgenic mice results in T-cell acute lymphoblastic leukemia/lymphoma. 150 13

We have cloned 70 kb of DNA from chromosome 11p13 at the site of a recurrent translocation in T-cell leukaemia (T-ALL): t(11;14)(p13;q11). The translocation involves the TCR-delta gene on 14q11 and a new site on 11p13. Two new and 10 previously identified translocations all mapped within 25 kb on 11p13, the 11p13 T-cell translocation cluster (11p13 ttc). A search for expressed sequences surrounding the breakpoint cluster region on 11p13 identified a gene telomeric of all breakpoints which is overexpressed in three T-ALL samples with a t(11;14). The gene T-cell translocation gene (TTG-2) encodes a small cysteine-rich protein. Forty-eight per cent of the amino acids are identical with another translocation-deregulated gene, TTG-1 (T-cell translocation gene 1 or rhombotin) in 11p15. There are two copies of a cysteine-rich motif in both proteins. Two tandem copies of the same cysteine-rich motif are also present in the recently described lin-11, isl-1 and mec-3 gene products, and one motif is found in the CRIP protein. Therefore the proteins encoded by these two translocation-deregulated genes belong to this new class of cysteine-rich proteins with the 'LIM' motif, which are important in normal development.
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PMID:TTG-2, a new gene encoding a cysteine-rich protein with the LIM motif, is overexpressed in acute T-cell leukaemia with the t(11;14)(p13;q11). 192 11

A chromosomal translocation in a T-cell leukemia involving the short arm of human chromosome 11 at band 11p15 disrupts the rhombotin gene. This gene encodes a protein with duplicated cysteine-rich regions called LIM domains, which show homology to zinc-binding proteins and to iron-sulfur centers of ferredoxins. Two homologues of the rhombotin gene have now been isolated. One of these, designated Rhom-2, is located on human chromosome 11 at band 11p13, where a cluster of T-cell leukemia-specific translocations occur; all translocation breakpoints at 11p13 are upstream of the Rhom-2 gene. Human and mouse Rhom-2 are highly conserved and, like rhombotin, encode two tandem cysteine-rich LIM domains. Rhom-2 mRNA is expressed in early mouse development in central nervous system, lung, kidney, liver, and spleen but only very low levels occur in thymus. The other gene, designated Rhom-3, is not on chromosome 11 but also retains homology to the LIM domain of rhombotin. Since the Rhom-2 gene is such a common site of chromosomal damage in T-cell tumors, the consistency of translocations near the rhombotin gene was further examined. A second translocation adjacent to rhombotin was found and at the same position as in the previous example. Therefore, chromosome bands 11p15 (rhombotin) and 11p13 (Rhom-2) are consistent sites of chromosome translocation in T-cell leukemia, with the 11p15 target more rarely involved. The results define the rhombotin gene family as a class of T-cell oncogenes with duplicated cysteine-rich LIM domains.
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PMID:The rhombotin family of cysteine-rich LIM-domain oncogenes: distinct members are involved in T-cell translocations to human chromosomes 11p15 and 11p13. 203 76

Recurrent chromosome translocations involving 11p13 and 14q11 are found in 5-10% of cases of T-ALL. The gene involved in the translocation on chromosome 14 is the T cell antigen receptor alpha or delta. The putative oncogene on chromosome 11 is rhombotin 2 (RBTN2)/translocated in T cell gene 2 (ttg-2), a member of the LIM family of proteins. In this paper we characterize a cell line KOPT-K1 that has a t(11;14)(p13;q11). The breakpoint on chromosome 11 involves an Alu-rich region with the break occurring between two Alu sequences on chromosome 11. In addition, approximately 70 bases from the break on chromosome 11 is a tetranucleotide repeat. Whether either of these structures played a role in the translocation is not known. No heptamer or nonamer sequences, implicated in other rearrangements were found near the breakpoint. The breakpoint on chromosome 11 maps more centromeric than previous translocations of this region. Despite this the RBTN2 gene is highly expressed in KOPT-K1. This cell line will be useful for investigating the role of RBTN2 in leukemogenesis and the mechanism by which the translocation alters the expression of RBTN2.
Leukemia 1995 Nov
PMID:Molecular characterization of a chromosome translocation breakpoint t(11;14)(p13;q11) from the cell line KOPT-K1. 747 67

Members of the human TTG/RBTN family, now renamed 'LMO' for LIM-only proteins, encode proteins with two tandem copies of a LIM motif. There are three members of this family, two have been isolated at the sites of chromosomal translocations in T-cell leukaemia. The function of the LIM motifs is at present unknown. We found that the LMO-2 gene is highly conserved between mammals, Drosophila and yeast. As a first step to obtain a model system for studying the function of the LIM motifs we have isolated the Drosophila homologue Dlmo. In contrast to mammals Drosophila appears to have only one lmo gene. A 2087 bp cDNA clone was isolated from a larval cDNA library, encoding a protein of 266 amino acids. A second transcript with an alternative 5' end was identified in RNA from embryos. The Drosophila lmo protein consists of two tandem copies of the conserved LIM domain characteristic of the human LMO family and an extended amino and carboxy terminus, which is not present in the human proteins. The amino acid sequence similarity with human LMO-1 and LMO-2 in LIM 1 is 79% and 69% and in LIM-2 90% and 60%, respectively. In addition a short stretch of 25 nucleotides with a homology of 83% between LMO-2 and Dlmo is found in the 3' UTR. Dlmo, like LMO-1, has an intron after the second LIM encoding region, which is not present in LMO-2. It is expressed maternally and at a high level in early embryogenesis as well as in adults. Interestingly we observed that the Dlmo protein is immunologically related to LMO-2 and can be detected by immunohistochemistry in early cellular blastoderm embryos. The gene was localised to a genetically well characterized region (17C on the X chromosome) opening the way for identification of mutations.
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PMID:A single ancestral gene of the human LIM domain oncogene family LMO in Drosophila: characterization of the Drosophila Dlmo gene. 747 48

The protein products of proto-oncogenes implicated in T cell acute lymphoblastic leukemia include two distinct families of presumptive transcription factors. RBTN1 and RBTN2 encode highly related proteins that possess cysteine-rich LIM motifs. TAL1, TAL2 and LYL1 encode a unique subgroup of basic helix-loop-helix (bHLH) proteins that share exceptional homology in their bHLH sequences. We have found that RBTN1 and RBTN2 have the ability to interact with each of the leukemogenic bHLH proteins (TAL1, TAL2 and LYL1). These interactions occur in vivo and appear to be mediated by sequences within the LIM and bHLH domains. The LIM-bHLH interactions are highly specific in that RBTN1 and RBTN2 will associate with TAL1, TAL2 and LYL1, but not with other bHLH proteins, including E12, E47, Id1, NHLH1, AP4, MAX, MYC and MyoD1. Moreover, RBTN1 and RBTN2 can interact with TAL1 polypeptides that exist in assembled bHLH heterodimers (e.g. TAL1-E47), suggesting that the RBTN proteins can influence the functional properties of TAL1. Finally, we have identified a subset of leukemia patients that harbor tumor-specific rearrangements of both their RBTN2 and TAL1 genes. Thus, the activated alleles of these genes may promote leukemia cooperatively, perhaps as a result of bHLH-LIM interactions between their protein products.
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PMID:Specific in vivo association between the bHLH and LIM proteins implicated in human T cell leukemia. 795 52

T cell acute leukaemias involve a number of different classes of oncogenes. A group of such genes is the RBTN family located on chromosomes 11 and 12. Two members of this family, RBTN1/Ttg-1 and RBTN2/Ttg-2, are located near recurring T cell acute lymphocytic leukaemia-associated translocations. Chromosomal translocations to both RBTN1/Ttg-1 and RBTN2/Ttg-2 involve T cell receptor (TCR) genes as result of an erroneous V(D)J joining process. RBTN1/Ttg-1 and RBTN2/Ttg-2 encode related proteins consisting of two cysteine-rich regions called LIM domains. The fact that LIM domains can be found with or without associated homeodomain led to the suggestion that the LIM domains may function as regulators of transcription, and that alterations of transcription networks, after chromosomal translocations, lead to leukaemia. This is a common feature that has been noted in the activation of transcription factors with a variety of structural motifs that include the basic helix-loop-helix motif and the homeodomain in leukaemias.
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PMID:LIM domain proteins in leukaemia and development. 814 20

Changes in protein phosphorylation in the human colon carcinoma cell line LIM 1215 after stimulation with epidermal growth factor (EGF) have been analyzed by two-dimensional gel electrophoresis and phosphoamino acid analysis. In addition to a number of tyrosine-phosphorylated proteins, a family of small proteins (M(r) 19,000-20,000) is maximally phosphorylated on serine within 5 min of EGF stimulation. One member of the family has been purified by a combination of two-dimensional electrophoresis and reversed-phase high performance liquid chromatography and identified by amino acid sequence analysis as stathmin. Although phosphorylation of stathmin has been reported previously in leukemia cells and following stimulation of hemopoietic or lymphoid cells with several mitogenic agents, this is the first report of stathmin phosphorylation in response to EGF.
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PMID:Epidermal growth factor induces serine phosphorylation of stathmin in a human colon carcinoma cell line (LIM 1215). 851 77

We describe the isolation of human LH-2, a putative transcription factor containing two cysteine-rich regions (LIM domains) and a homeobox (Hox) DNA-binding domain. High levels of hLH-2 expression were observed in all cases of chronic myelogenous leukaemia (CML) tested, regardless of disease status. hLH-2 was mapped to chromosome 9Q33-34.1, in the same region as the reciprocal translocation that creates the BCR-ABL chimera of the Philadelphia chromosome (Ph'), the hallmark of CML; hLH-2 was retained on the derivative 9 chromosome and is therefore centromeric of c-ABL. The proximity of hLH-2 to the breakpoint on chromosome 9 raises the possibility of cis-activation by the t(9;22)(q34;q11) translocation. In addition to finding hLH-2 expression in all cases of CML, expression was observed in lymphoid malignancies and myeloid cell lines, but not in primary cases of acute myelogenous leukaemia. The role of hLH-2 in the development or progression of leukaemia is not known. However, hLH-2 may prove useful as a marker of CML for monitoring residual disease.
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PMID:Identification of a human LIM-Hox gene, hLH-2, aberrantly expressed in chronic myelogenous leukaemia and located on 9q33-34.1. 864 22


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