Disease relevance of TRA@

• A small immature subgroup of CD3- T-ALL (n = 5) had both TCRG genes in germline configuration, three of them having also germline TCRD genes [1].
• Thirty T cell receptor (TCR)gammadelta+ T cell acute lymphoblastic leukemias (T-ALL) were analyzed for their immunophenotype, as well as for the rearrangements and junctional regions of the TCRG and TCRD genes [2].
• Subsequently, we evaluated, whether heteroduplex PCR analysis of rearranged TCRG and TCRD genes can be used for reliable identification of PCR targets for detection of minimal residual disease (MRD) [3].
• Application of the new FISH assays to a series of 24 angioimmunoblastic and 12 cutaneous T-cell lymphomas confirmed the cytogenetic evidence of lack of breakpoints in the TCRA/D or TCRB locus [4].
• 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 [5].

High impact information on TRA@

• Unacceptably high vaginal toxicity was reached at a TRA concentration of 0.484% [6].
• A phase I trial was conducted of the vitamin A derivative beta-all-trans-retinoic acid (vitamin A acid; TRA), delivered via a collagen sponge and cervical cap for mild or moderate intraepithelial cervical neoplasia [6].
• A concentration of 0.372% TRA is recommended for use in phase II trials in mild and moderate cervical intraepithelial neoplasia [6].
• TCR alpha (TCRA), TCR gamma (TCRG), and TCR beta (TCRB) loci were investigated by restriction fragment length polymorphism analysis [7].
• Recombinations placed the locus between framework markers D14S72 and MYH7, a 10-cM interval in which the markers D14S742, D14S50, D14S283, and TCRA showed no recombinations with the phenotype [8].

Chemical compound and disease context of TRA@

• Between April 1993 and June 1994, 29 patients (pts) with unresectable, locally advanced, or metastatic non-small cell lung cancer were treated with a combination of p.o. trans-retinoic acid (TRA), 150 mg/m2/day, in three divided doses and s.c. IFN-alpha, 3 x 10(6) units/day [9].
• Twenty-nine chemotherapy-naive patients with primary hepatocellular carcinoma were treated with oral beta-all trans-retinoic acid (retinoic acid, TRA 50 mg/m2 t.i.d.) on a 3-week on/one week off schedule until progression or grade 3 or 4 toxicity [10].
• The greatest increase in uptake following sepsis was among the gluconeogenic precursor amino acids alanine, glycine, threonine, and serine (CON, 27.0 +/- 4.2 mumol/g liver protein, TRA, 38.8 +/- 8.9 mumol/g liver protein; CLP, 62.8 +/- 6.0 mumol/g liver protein).(ABSTRACT TRUNCATED AT 250 WORDS)[11]
• These included (i) 14 controls; (ii) 23 patients with Graves' disease who were tested for TRA within 3 months of commencing treatment with carbimazole of which 13 were studied serially; (iii) 5 patients with toxic nodular goitre; (iv) 4 with euthyroid exophthalmos; and (v) 2 neonates of thyrotoxic mothers [12].

Biological context of TRA@

• The clonal TCRB, TCRG and TCRD gene rearrangements were analyzed for gene segment usage and for the size and composition of their junctional regions [13].
• T-cell prolymphocytic leukaemia (T-PLL) is a sporadic, mature T-cell disorder in which there is usually an aberrant T-cell receptor alpha (TCRA) rearrangement that activates the TCL1 or MTCP1-B1 oncogenes [14].
• Only eight of the 17 enzymes examined revealed restriction fragment length polymorphism (RFLP), with the use of TCRA, TCRB, and TCRG [15].
• TCRG genes are rearranged first, subsequently TCRB genes are rearranged, followed by TCRA gene activation [16].
• Incidence of the predominant TCRD Vdelta2-Ddelta3 rearrangement decreases with age but is independent of genotype [17].

Anatomical context of TRA@

• We resequenced all 57 variable (V) genes in the human T cell receptor alpha and delta (TRA/TRD) locus in 40 individuals of Northern European, Mexican, African-American and Chinese descent [18].
• Apparently, some parts of the TCRD (Vdelta2-Ddelta region) and TCRG genes are accessible for recombination not only in T cells, but also in early B-cells and even in nonlymphoid cells if the appropriate transcription factors are present [19].
• Trans-rearrangements between TCRG and TCRD loci, similar in structure and frequency to those observed previously in human lymphoid tissues, were demonstrated in normal mouse thymus by PCR with crossed V gamma/J delta and V delta/J gamma primer pairs [20].
• A total of 54 primers was developed (1) to amplify rearrangements of the TCRD, TCRG, and IGK (Kde) genes as well as TAL1 deletions; (2) to sequence the junctional regions and breakpoint fusion regions; and (3) to perform MRD detection in bone marrow or peripheral blood samples during follow-up of ALL patients [21].
• To determine the sensitivity of heteroduplex analysis with renaturation at 4 degrees C, (c)DNA of T cell malignancies with proven clonal rearrangements was serially diluted in (c)DNA of polyclonal mononuclear peripheral blood cells and amplified using V and C primers (TCRB genes) or V and J primers (TCRG and TCRD genes) [22].

Associations of TRA@ with chemical compounds

• In order to evaluate the influence of vesicle structure on the photostability of tretinoin, TRA-loaded vesicles were prepared by the film hydration method, extrusion technique and sonication [23].
• After UV irradiation, TRA dissolved in methanol degraded very quickly while the incorporation in vesicles always led to a reduction of the photodegradation process [23].
• However, the inclusion of TRA in P90H liposomes and Brij 30 or Triton CG110 niosomes retarded the drug photodegradation [23].
• METHODS: We used polymerase chain reaction (PCR) for amplification of junctional region of rearranged IgH, TCRD and TCRG genes in combination with heteroduplex analysis in polyacrylamide gel [24].
• By using in situ chromosomal hybridization and Southern blot analysis to examine RPMI 8402 cells, we determined that the break at 14q11 occurs within the variable region sequences of the T-cell receptor alpha-chain gene (TCRA); the break at 11p15 occurs between the HRAS1 gene and the genes for insulin and the insulin-like growth factor 2 [25].

Other interactions of TRA@

• Here, we identified chromosomal translocations targeting the CCND2 locus at 12p13, and the T-cell receptor beta (TCRB) or the TCRA/D loci in T-cell acute lymphoblastic leukemias (T-ALLs) [26].
• The pattern of amino acid usage in the CDR3 region is dissimilar between TCRA and TCRB transcripts [27].
• One type of T-cell leukemia, T-cell prolymphocytic leukemia, is consistently associated with chromosome rearrangements characterized by the juxtaposition of the TCRA locus on chromosome 14q11 and either the TCL1 gene on 14q32.1 or the MTCP1 gene on Xq28 [28].
• CONCLUSION: These linkage studies provide no significant evidence of a major germline-encoded TCRA or TCRB component of susceptibility to RA [29].
• We investigated the TCRA and TCRB chain genes of HLA-typed Belgian CP MS patients employing four DNA restriction fragment length polymorphisms (RFLPs) detected with TCR constant (TCRAC1, TCRBC2) and variable (TCRBV8, TCRBV11) gene segments [30].

Analytical, diagnostic and therapeutic context of TRA@

• Combined Southern blot and PCR data for IGH, IGK-Kde, and TCRD genes showed significant differences in stability at relapse between monoclonal and oligoclonal rearrangements: 89% versus 40%, respectively [31].
• Simultaneous detection of TCRA/D or TCRB breaks was achieved in a multicolor approach, which was further combined with detection of the T-cell-specific CD3 antigen in a multicolor FICTION (Fluorescence Immunophenotyping and Interphase Cytogenetics as a Tool for the Investigation of Neoplasm) assay [4].
• L540 was studied by in situ hybridization for chromosomal rearrangements concerning the regions where genes for TCRA and TCRB chains, for MET oncogene, and for rRNA are located [32].
• Comparative sequence analysis of the human T cell receptor TCRA and TCRB CDR3 regions [33].
• These results show the validity and reliability of the fluorescent PCR method for routine detection of IGH, TCRG and TCRD rearrangements [34].

References