Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UMLS:C0023418 (leukemia)
93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two members of the RBTN gene family, RBTN1/Ttg-1 and RBTN2/Ttg-2, were found by their association with T-cell tumour-specific chromosomal translocations and are thought to be involved in the aetiology of such T-cell tumours. Here a transgenic mouse model is described in which T-cell tumours are induced by the presence of RBTN1 and RBTN2 transgenes that direct expression in thymus-derived cells. The latency period for lymphoid tumour appearance is variable, and tumours occur in a small proportion of transgenic animals that develop T-cell acute lymphoblastic malignancies. No significant increase in the rate of tumour development was observed in RBTN1 transgenic mice infected with Moloney murine leukaemia virus, nor did tumours arise in mice bearing a construct in which RBTN1 was expressed from the insulin transcriptional promoter. These data, which provide formal proof of the oncogenic activity of these genes, suggest that aberrant expression of transcription factor genes, such as RBTN1 and RBTN2, functions in tumour aetiology by disturbing some aspect of T-cell differentiation.
...
PMID:T-cell acute lymphoblastic lymphoma induced in transgenic mice by the RBTN1 and RBTN2 LIM-domain genes. 146 47

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.
...
PMID:The rhombotin gene family encode related LIM-domain proteins whose differing expression suggests multiple roles in mouse development. 150 24

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

Rhombotin-2 (RBTN-2) is a LIM domain protein that, with the exception of thymocytes, is widely expressed during fetal development. Although RBTN-2 is crucial for normal erythropoiesis, the ectopic expression of RBTN-2 in T lymphocytes results in T-cell proliferation and leukemogenesis. Thus, while a proliferative function for RBTN-2 has been established in T-cells, neither its role in erythropoiesis nor its function(s) in other tissues are known. We have examined the expression and location of RBTN-2 in normal and malignant cells. Similar to fetal development, RBTN-2 RNA was detected in all normal adult tissues tested with the exception of colon and thymocytes. RBTN-2 RNA was not detected in all primary tumors and tumor cell lines, indicating RBTN-2 expression is not ubiquitous in proliferating cells. Using polyclonal antisera, RBTN-2 was detected predominantly in the nucleus of human hematopoietic cells. Significantly, human leukemic T cells with disruption of the RBTN-2 locus and thymocytes from transgenic mice with enforced expression of RBTN-2 showed similar nuclear location of RBTN-2 protein, consistent with the notion that RBTN-2 acts as a transcriptional regulator in T-cell proliferation. Surprisingly, in normal tissues, RBTN-2 showed a strikingly similar distribution to that of metallothionein-1, having both nuclear and cytoplasmic localization that suggested that RBTN-2 may be involved in the acute phase response. Indeed, similar to metallothionein-1, RBTN-2 mRNA was induced in thymocytes of mice exposed to zinc and in human thymocytes treated with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate. Since the LIM domain permits binding of multiple protein partners, the specific function of RBTN-2 may depend upon subcellular sequestration through interaction with different cofactors. Thus, in addition to its roles in erythropoiesis and T-cell leukemia, RBTN-2 may also be involved in the acute phase response.
...
PMID:Expression of the proto-oncogene rhombotin-2 is identical to the acute phase response protein metallothionein, suggesting multiple functions. 754 55

The RBTN2 LIM-domain protein, originally identified as an oncogenic protein in human T-cell leukemia, is essential for erythropoiesis. A possible role for RBTN2 in transcription during erythropoiesis has been investigated. Direct interaction of the RBTN2 protein was observed in vivo and in vitro with the GATA1 or -2 zinc-finger transcription factors, as well as with the basic helix-loop-helix protein TAL1. By using mammalian two-hybrid analysis, complexes involving RBTN2, TAL1, and GATA1, together with E47, the basic helix-loop-helix heterodimerization partner of TAL1, could be demonstrated. Thus, a molecular link exists between three proteins crucial for erythropoiesis, and the data suggest that variations in amounts of complexes involving RBTN2, TAL1, and GATA1 could be important for erythroid differentiation.
...
PMID:Association of erythroid transcription factors: complexes involving the LIM protein RBTN2 and the zinc-finger protein GATA1. 756 77

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.
...
PMID:Specific in vivo association between the bHLH and LIM proteins implicated in human T cell leukemia. 795 52

RBTN2 is a LIM domain protein which can be activated by the translocation t(11;14)(p13;q11) in childhood T cell acute leukaemia. Transgenic mice were examined in which rbtn2 protein is expressed in the T cell lineage. An average of 72% of these mice developed T cell tumours before 18 months of age, compared with 9% in transgenic mice expressing the related gene Rbtn-1. Rbtn2-induced tumours first appeared at 5 months of age and were clonal. They displayed a range of phenotypes, the most notable being CD3/CD45R double-positive cells. Tumours expressing either T cell receptor alpha/beta or gamma/delta heterodimers were found. Thus rbtn2 can promote tumours within a range of T cell types and maturities. The latency period before tumour development indicates that secondary events must occur before the onset of overt malignancy.
...
PMID:T cell tumours of disparate phenotype in mice transgenic for Rbtn-2. 797 Jul 26

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.
...
PMID:LIM domain proteins in leukaemia and development. 814 20

The LMO2 and TAL1 genes were first identified via chromosomal translocations and later found to encode proteins that interact during normal erythroid development. Some T cell leukaemia patients have chromosomal abnormalities involving both genes, implying that LMO2 and TAL1 act synergistically to promote tumorigenesis after their inappropriate co-expression. To test this hypothesis, transgenic mice were made which co-express Lmo2 and Tal1 genes in T cells. Dimers of Lmo2 and Tal1 proteins were formed in thymocytes of double but not single transgenic mice. Furthermore, thymuses of double transgenic mice were almost completely populated by immature T cells from birth, and these mice develop T cell tumours approximately 3 months earlier than those with only the Lmo2 transgene. Thus interaction between these two proteins can alter T cell development and potentiate tumorigenesis. The data also provide formal proof that TAL1 is an oncogene, apparently acting as a tumour promoter in this system.
...
PMID:Protein dimerization between Lmo2 (Rbtn2) and Tal1 alters thymocyte development and potentiates T cell tumorigenesis in transgenic mice. 860 71

The rhombotin 2 gene was identified by its association with a recurrent chromosome translocation (11;14)(p13;q11), occurring in T-cell acute lymphoblastic leukaemias (ALLs). High levels of RBTN2 have been found in T-cell leukaemias carrying the translocation and in some T-cell ALLs that lack, by cytogenetic and molecular techniques, translocations involving 11p13. In normal murine tissues RBTN2 has been found to be widely expressed, with high levels present in brain and early B cells. Studies carried out in mice lacking RBTN2 have demonstrated the importance of this gene in erythropoiesis. We have investigated the expression of RBTN2 in human leukaemic cells, and in human and murine normal myeloid progenitor cells. RBTN2 is expressed in the leukaemic cells of patients with pre-B ALL, T-ALL and acute myeloblastic leukaemia (AML). By cytogenetic and molecular techniques no abnormalities were noted in 11p13. Using clonogenic assays and single cell PCR we found that RBTN2 is expressed strongly in the precursors of mixed erythrocyte/macrophage/mast, erythrocyte, megakaryocyte, neutrophil and macrophage colonies. In contrast, RBTN2 message was low to undetectable in the mature progeny. These findings indicate that RBTN2 is expressed in leukaemias of both the myeloid and lymphoid lineages. Further, these studies show that in normal myeloid and lymphoid cells the expression of RBTN2 is present in progenitor cells and is lost as the cells terminally differentiate. This latter finding further illustrates that the detection of a RNA in a population of cells should not be interpreted to mean that all of the cells in that population express the RNA.
...
PMID:Expression of rhombotin 2 in normal and leukaemic haemopoietic cells. 863 17


1 2 3 4 5 6 7 8 9 10 Next >>

---