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)

T-cell acute lymphoblastic leukemia (T-ALL) is associated with chromosomal aberrations characterized by juxtaposition of proto-oncogenes to T-cell receptor gene loci (TCR), resulting in the deregulated transcription of these proto-oncogenes. Here, we describe the molecular characterization of a novel chromosomal aberration, inv(14)(q11.2q32.31), in a T-ALL sample, involving the recently described BCL11B gene and the TCRD locus. The inversion joined the 5' part of BCL11B, including exons 1-3, to the TRDD3 gene segment of the TCRD locus, whereas the reciprocal breakpoint fused the TRDV1 gene segment to the fourth exon of BCL11B. The TRDV1-BCL11B joining region was 1344 bp long and contained fragments derived from 20q11.22, 3p21.33 and from 11p12, indicating the complex character of this aberration. A strong expression of in-frame transcripts with truncated BCL11B and TCRD constant region (TRDC) were observed, but in contrast to normal T cells and other T-ALL samples, no wild-type BCL11B transcripts were detected in the T-ALL sample. Screening of 37 other T-ALLs revealed one additional case with expression of the BCL11B-TRDC fusion transcript. As BCL11B appears to play a key role in T-cell differentiation, BCL11B disruption and disturbed expression may contribute to the development of T-cell malignancies in man.
Leukemia 2005 Feb
PMID:Disruption of the BCL11B gene through inv(14)(q11.2q32.31) results in the expression of BCL11B-TRDC fusion transcripts and is associated with the absence of wild-type BCL11B transcripts in T-ALL. 1566

Umbilical cord blood (CB) has been used as a valuable source of hematopoietic stem cells for allogeneic transplantation, specific CTL response and immunotherapy for decades. We previously analyzed the distribution and clonality of T-cell receptor alpha and beta variable region (TRAV) and (TRBV) of the subfamily T cell receptors in T cells from umbilical cord blood. Recent data indicated that gammadelta(+) T cells may play an important role in mediating the graft versus leukemia effect after stem cells transplantation and in anti-cancer response. In order to further characterize the repertoire of CB T-cells, the frequency of alphabeta(+) and gammadelta(+) T cells were examined in CB by FACS. The CDR3 size of 4 TRGV and 8 TRDV subfamily genes were analyzed in mononuclear cells (MCs) from 16 CB samples, using RT-PCR and genescan technique. To determine the expression level of TRGV subfamily genes, we performed quantitative analysis of TRGVI-III subfamilies by real-time PCR. Low percentage of CD3(+)TCRgammadelta(+) cells was observed in CB. The frequency of expression in TRGVI, TRGVII and TRGVIII in CBMCs was 93.75%, 81.25% and 56.25%, respectively. The mean value of the number of expressed TRDV subfamilies in CBMCs is higher than that from adult peripheral blood (PB) group. The frequently expressed members in CB were TRDV1 (100%), TRDV2 (93.75%), TRDV8 (93.75%) and TRDV3 (81.25%), respectively. The frequencies of TRDV5 and TRDV8 in CBMCs were significantly higher than those from PBMCs. Most of the PCR products of TRGV and TRDV subfamilies from 10 CB samples displayed polyclonal rearrangement pattern, whereas one or two PCR products from 6 CB samples showed oligoclonality or biclonality. In contrast, PCR products from 9 of 10 adult healthy controls contained at least an oligoclonal peak in different TRGV or TRDV subfamilies respectively. The pattern of TRGV subfamily expression level in CBMCs was TRGVI>TRGVIII>TRGVII, and in contrast, TRGVII>TRGVI>TRGVIII was found in PBMCs. In conclusion, our results indicate polyclonal and more diverse TRDV segment usage in CB gammadelta(+) T-cells. The pattern of TRGV expression levels in CB T cells was found to be quite different from the one in PB T cells. These findings are apparently the first report regarding the repression pattern of TRGV repertoire in CB. It also provides a detailed profile of the global TRGV and TRDV repertoire and TRGVI-III expression levels in cord blood T cells in Chinese subjects. The biological significance of the differences observed between CB and PB is at present obscure. However, this study will definitively contribute to understand the cellular immune features better and to exploit more efficiently the therapeutic potentials of CB.
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PMID:TRGV and TRDV repertoire distribution and clonality of T cells from umbilical cord blood. 1901 41