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

TAL1 gene rearrangement is the most common genetic defect associated with T cell acute lymphoblastic leukaemia (T-ALL). Tumour-specific rearrangements of TAL1 arise as a result of either chromosome translocation or local DNA recombination. TAL1 gene products possess the basic helix-loop-helix (bHLH) motif, a DNA-binding domain common to several known transcription factors. The bHLH domain of TAL1 is especially homologous to those encoded by TAL2 and LYL1, distinct genes that were also identified on the basis of chromosomal rearrangement in T-ALL. Thus, TAL1, TAL2 and LYL1 constitute a unique family of bHLH proteins, each of which is a potential mediator of T cell leukaemogenesis.
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PMID:TAL1, TAL2 and LYL1: a family of basic helix-loop-helix proteins implicated in T cell acute leukaemia. 814 19

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

Recombinant murine leukemia viruses from the highly leukemic mouse strains AKR, HRS, and C58 usually acquire pathogenic U3 region sequences fro the endogenous xenotropic virus, Bxv-1. However, the majority of tumors from another highly leukemic strain, CWD, contained recombinant viruses that lacked Bxv-1-specific sequences. The nucleotide sequence of the U3 regions of two such CWD recombinants was nearly identical to that of the endogenous ecotropic virus parent Emv-1, but they shared three nucleotide substitutions immediately 3' of the enhancer core. These substitutions were found in recombinant proviruses from about one-third of spontaneous CWD lymphomas as determined by an oligonucleotide hybridization assay of proviral fragments that had been nucleotide substitutions in the CWD viruses were inherited from an endogenous polytropic provirus that is absent in the other highly leukemic strains. On the basis of the results of these and previous studies, we propose that CWD recombinants acquire pathogenic U3 region sequences through recombination with an endogenous polytropic virus or Bxv-1 and that the pathogenicity of these sequences may be related to a sequence motif that is known to bind members of the basic helix-loop-helix class of transcription factors.
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PMID:Origins of enhancer sequences of recombinant murine leukemia viruses from spontaneous B- and T-cell lymphomas of CWD mice. 818 15

The transcriptionally regulatory regions of the lymphomagenic Akv and SL3-3 murine leukemia retroviruses (MLVs) contain two types of E-box consensus motifs, CAGATG. One type, EA/S, is located in the upstream promoter region, and the other, E(gre), is located in a tandem repeat with enhancer properties. We have examined the requirements of the individual E-boxes in MLV transcriptional regulation. In lymphoid cell lines only, the E(gre)-binding protein complexes included ALF1 or HEB and E2A basic helix-loop-helix proteins. Ectopic ALF1 and E2A proteins required intact E(gre) motifs for mediating transcriptional activation. ALF1 transactivated transcription of Akv MLV through the two E(gre) motifs equally, whereas E2A protein required the promoter-proximal E(gre) motif. In T- and B-cell lines, the E(gre) motifs were of major importance for Akv MLV transcriptional activity, while the EA/S motif had some effect. In contrast, neither E(gre) nor EA/S motifs contributed pronouncedly to Akv MLV transcription in NIH 3T3 cells lacking DNA-binding ALF1 or HEB and E2A proteins. The Id1 protein was found to repress ALF1 activity in vitro and in vivo. Moreover, ectopic Id1 repressed E(gre)-directed but not EA/S-directed MLV transcription in lymphoid cell lines. In conclusion, E(gre) motifs and interacting basic helix-loop-helix proteins are important determinants for MLV transcriptional activity in lymphocytic cell lines.
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PMID:Various modes of basic helix-loop-helix protein-mediated regulation of murine leukemia virus transcription in lymphoid cell lines. 870 9

The human T-cell leukemia virus-encoded oncoprotein Tax is a potent deregulator of cellular gene expression. Here we report that Tax represses transcription of the human bax gene, a gene whose protein product accelerates apoptosis. This repression is mediated through a 27-bp sequence in the bax promoter that contains a putative basic helix-loop-helix binding site. Deletion of this sequence abolishes Tax-mediated repression of bax. Repression of the bax gene may be biologically significant, as we also show that HTLV-I-infected cell lines are resistant to a variety of physical, chemical, and biological stimuli which induce apoptosis in uninfected T-cells. The repression of genes involved in promoting apoptosis, including the bax gene, may contribute to retroviral survival, and initiate a pathway toward malignant transformation.
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PMID:Repression of bax gene expression by the HTLV-1 Tax protein: implications for suppression of apoptosis in virally infected cells. 914 12

The LIM-only protein Lmo2, originally identified as an oncogenic protein in human T cell leukemia, is essential for erythropoiesis. A possible role for Lmo2 in transcription during erythropoiesis has been investigated. Direct interaction of Lmo2 was observed in vitro and in vivo with the zinc finger transcription factor GATA-1, as well as with the basic helix-loop-helix (bHLH) transcription factor Tall. By using mammalian two-hybrid analysis, E47/Tall/Lmo2/GATA-1 protein complex could be demonstrated. Thus, a molecular link exists between three proteins crucial for erythropoiesis. This data suggest that variations in amounts of complexes involving Lmo2, Tall, and GATA-1 could be important for erythroid differentiation.
Leukemia 1997 Apr
PMID:LIM-only protein Lmo2 forms a protein complex with erythroid transcription factor GATA-1. 920 74

tal-1 (T-cell acute leukemia-1; also known as SCL) and tal-2 genes belong to a family of basic helix-loop-helix transcription factors and were originally isolated from the breakpoints of chromosomal translocations in human T-cell leukemia cell lines. tal-1 is expressed not only in hematopoietic cells but also in several endothelial structures and the central nervous system during development. On the other hand, the detailed function and the sites of expression of tal-2 have remained obscure. We cloned the tal-2 cDNA from a mouse embryonic cDNA library and examined its expression pattern in the mouse, comparing with that of tal-1. In situ analyses revealed that tal-2 transcripts are detected at embryonic day 12.5 in the following regions; 1) the diencephalon-the zona limitans intrathalamica and the pretectum, 2) the mesencephalon-the tectum, and the anterior and posterior tegmentum, 3) the metencephalon-the isthmus and the anterior pons. In the diencephalon and the mesencephalon, the expression sites of tal-2 gene were similar to those of tal-1, and its expression was stronger than that of tal-1. In the metencephalon, tal-2 expression was observed in the anterior pons, whereas tal-1 transcripts were detected in the entire pons, and showed stronger expression than tal-2. The tal-2 messages were barely detectable in the brain at birth. These results suggest that tal-1 and tal-2 are involved in the development of specific areas of the central nervous system.
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PMID:The leukemic oncogene tal-2 is expressed in the developing mouse brain. 993 88

Hematopoietic development is regulated in large part by transcription factors that control cell fate decisions and cellular differentiation. Several genes first discovered in the context of chromosomal translocations in leukemia also serve important functions in blood cell development. Gene-targeting experiments related to two of these factors, SCL/tal-1 and translocation-ets-leukemia (TEL), are reviewed here. SCL/tal-1, a T-cell basic helix-loop-helix oncoprotein, is required for the formation of all hematopoietic lineages. In addition, it is essential for angiogenesis in the yolk sac, indicating a dual function in blood and vessel development. TEL, an ets-related factor which is translocated to a variety of other genes in leukemias, is also required for proper angiogenesis in the yolk sac. Additional studies, however, demonstrate that TEL function is necessary for hematopoiesis to be established in the bone marrow microenvironment. These studies emphasize the intrinsic roles of leukemia-associated transcription factors in normal blood cell and vessel development.
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PMID:Intersections between blood cell development and leukemia genes. 1019 97

The stem cell leukaemia (SCL) gene is a member of the basic helix-loop-helix family of transcription factors and is essential for the development of all haematopoietic lineages. SCL is expressed in pluripotent haematopoietic stem cells and also following commitment to the erythroid, mast and megakaryocytic lineages. The mechanisms responsible for this pattern of expression are poorly understood, but are likely to illuminate the molecular basis for stem cell development and lineage commitment. Here we present the first description of the regulation of the SCL gene in mast cells. In this study we systematically analysed the chromatin structure of a 45 kb region of the murine SCL locus in mast cells. The pattern of DNase 1 and restriction endonuclease hypersensitive sites in mast cells was distinct from, but overlapped with, the pattern previously described in erythroid and primitive myeloid cells. Each potential regulatory element was tested using transient reporter assays to assess their functional significance in mast cells. These studies identified two potent enhancers, one of which was downstream of the SCL gene. Further characterisation of this 3' enhancer demonstrated that it required the presence of two distinct DNase 1 hypersensitive sites for full activity, and that it was capable of stimulating transcription from both promoter 1a and 1b. Since the 3' enhancer is active in both erythroid and mast cells, it will now be important to see whether it is independently activated in these lineages, or whether it is also active in haematopoietic stem cells.
Leukemia 1999 May
PMID:Chromatin structure and transcriptional regulation of the stem cell leukaemia (SCL) gene in mast cells. 1037 80

The t(1;19) chromosomal translocation of pediatric pre-B cell leukemia produces chimeric oncoprotein E2a-Pbx1, which contains the N-terminal transactivation domain of the basic helix-loop-helix (bHLH) transcription factor, E2a, joined to the majority of the homeodomain protein, Pbx1. There are three Pbx family members, which bind DNA as heterodimers with both broadly expressed Meis/Prep1 homeo-domain proteins and specifically expressed Hox homeodomain proteins. These Pbx heterodimers can augment the function of transcriptional activators bound to adjacent elements. In heterodimers, a conserved tryptophan motif in Hox proteins binds a pocket on the surface of the Pbx homeodomain, while Meis/Prep1 proteins bind an N-terminal Pbx domain, raising the possibility that the tryptophan-interaction pocket of the Pbx component of a Pbx-Meis/Prep1 complex is still available to bind trypto-phan motifs of other transcription factors bound to flanking elements. Here, we report that Pbx-Meis1/Prep1 binds DNA cooperatively with heterodimers of E2a and MyoD, myogenin, Mrf-4 or Myf-5. As with Hox proteins, a highly conserved tryptophan motif N-terminal to the DNA-binding domains of each myogenic bHLH family protein is required for cooperative DNA binding with Pbx-Meis1/Prep1. In vivo, MyoD requires this tryptophan motif to evoke chromatin remodeling in the Myogenin promoter and to activate Myogenin transcription. Pbx-Meis/Prep1 complexes, therefore, have the potential to cooperate with the myogenic bHLH proteins in regulating gene transcription.
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PMID:A conserved motif N-terminal to the DNA-binding domains of myogenic bHLH transcription factors mediates cooperative DNA binding with pbx-Meis1/Prep1. 1047 46


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