Disease relevance of Gene Rearrangement

• The 0.74-kb cDNA probe detected DNA rearrangements in the MLL gene in 58 of the patients with leukemia, in the 3 cell lines, and in 3 of the patients with lymphoma [1].
• Selection for T-cell receptor V beta-D beta-J beta gene rearrangements with specificity for a myelin basic protein peptide in brain lesions of multiple sclerosis [2].
• This demonstrates that "toxicity" of bi-allelic H chain expression and cell-autonomous mechanisms of silencing in-frame IgH gene rearrangements do not significantly contribute to allelic exclusion at the IgH locus [3].
• T cell rearranging gene gamma (TRG gamma) and T cell antigen receptor beta (TCR beta) chain gene rearrangement and transcription were studied in a series of patients with B-lineage acute lymphoblastic leukemia (ALL), in which the Ig H chain genes are rearranged and the surface phenotype reproduces the stages of normal pre-B maturation [4].
• Twelve cases of T gamma LPD (lymphoproliferative disorders of Fc gamma receptor-bearing T cells) involving an expansion of large granular lymphocyte/natural killer (LGL/NK) cells were investigated for the expression of LGL/NK-associated markers and for T beta gene rearrangement [5].

Psychiatry related information on Gene Rearrangement

• A detailed analysis of the MECP2 gene: prevalence of recurrent mutations and gross DNA rearrangements in Rett syndrome patients [6].

High impact information on Gene Rearrangement

• Finally, IRF4 and IRF8 together control the termination of pre-B cell receptor signaling and thus promote differentiation to small pre-B cells undergoing light-chain gene rearrangements [7].
• The generation of the earliest B cell progenitors depends on E2A and EBF, which coordinately activate the B cell gene expression program and immunoglobulin heavy-chain gene rearrangements at the onset of B-lymphopoiesis [7].
• The products of three of the genes--IL-2RG, Jak3, and IL-7R alpha--are components of cytokine receptors, and the products of three more-RAG1, RAG2, and Artemis-are essential for effecting antigen receptor gene rearrangement [8].
• Thus, mere membrane deposition of Ig, even with concomitant expression of bcl-2, terminates neither expression of RAG-1 and 2, nor secondary L chain gene rearrangements, nor does it allow the development of mature B cells [9].
• However, recent findings suggest that early B cell development can occur without expression of surrogate L chain, without deposition of microH chains into membranes, without productive H chain gene rearrangements, and even without any rearrangements of Ig gene loci [9].

Chemical compound and disease context of Gene Rearrangement

• Modification of DNA by glucose 6-phosphate induces DNA rearrangements in an Escherichia coli plasmid [10].
• Human homologue of the rat chondroitin sulfate proteoglycan, NG2, detected by monoclonal antibody 7.1, identifies childhood acute lymphoblastic leukemias with t(4;11)(q21;q23) or t(11;19)(q23;p13) and MLL gene rearrangements [11].
• Characterization of a DNA topoisomerase IIalpha gene rearrangement in adriamycin-resistant P388 leukemia: expression of a fusion messenger RNA transcript encoding topoisomerase IIalpha and the retinoic acid receptor alpha locus [12].
• Both MEN 2 mutations and PTC gene rearrangements potentiate the intrinsic tyrosine kinase activity of RET and, ultimately, activate the RET downstream targets [13].
• RET/PTC (rearranged in transformation/papillary thyroid carcinomas) gene rearrangements are the most frequent genetic alterations identified in papillary thyroid carcinoma [14].

Biological context of Gene Rearrangement

• A constitutively activated form of Notch produces a reciprocal phenotype and induces thymocytes that have functional gammadeltaTCR gene rearrangements to adopt the alphabeta T cell fate [15].
• Immunoglobulin heavy-chain class switching in a pre-B cell line is accompanied by DNA rearrangement [16].
• Telomeric antigen genes can be expressed without apparent DNA rearrangement, but they can also, like non-telomeric genes, have access to the telomeric expression site through a duplicative transposition mechanism resembling gene conversion [17].
• Run-on transcription experiments were used to demonstrate that transcription of T cell receptor beta chain V genes is activated by DNA rearrangement, in a manner similar to immunoglobulin genes [18].
• In order to investigate the possibility that recognition of these conserved sequences may sometimes permit intergenic joining of segments among different antigen receptor genes, DNA of normal human lymphoid tissues was examined by polymerase chain reaction amplification for the presence of chimeric gamma-delta T cell receptor gene rearrangements [19].

Anatomical context of Gene Rearrangement

• Purified surface lg-positive B cells, Lyt 2-positive mature T cells, and thymocytes transcribed the foreign mu gene at a similarly high level, suggesting that control of lg gene rearrangement might be the only mechanism that determines the specificity of heavy chain gene expression within the lymphoid cell lineage [20].
• We show that the vast majority of gamma/delta cells from M. leprae lesions use either V delta 1-J delta 1 or V delta 2-J delta 1 gene rearrangements and, within a given region of the lesion, display limited junctional diversity [21].
• Tumor-infiltrating lymphocytes (TILs) grown in the presence of IL-2 for 15-26 days had detectable T-cell receptor beta-chain gene rearrangements, which indicated oligoclonal enhancement in culture in four of nine TIL samples [22].
• The only clinical correlates that were significantly associated with TAL1 gene rearrangements were higher white blood cell count (P = .017) and higher hemoglobin (P = .007) at diagnosis [23].
• Either CD2+, CD3- NK cells are derived from a non-T lineage, or they have diverged from the T cell lineage earlier than the stage of T gamma gene rearrangement and CD3 delta chain expression; they are refractory to many induction signals in undergoing further T cell differentiation [24].

Associations of Gene Rearrangement with chemical compounds

• Using this assay with Abelson virus-transformed murine pre-B cells, we have found that bacterial lipopolysaccharide treatment, which activates transcription of the unrearranged kappa constant region gene, also activates kappa gene rearrangement [25].
• An active v-abl protein tyrosine kinase blocks immunoglobulin light-chain gene rearrangement [26].
• Brief actinomycin D treatment of conjugating cells blocked M-element excision, providing evidence that transcription is important for efficient DNA rearrangement [27].
• Transient IL-7/IL-7R signaling provides a mechanism for feedback inhibition of immunoglobulin heavy chain gene rearrangements [28].
• Since CHX and A23187 mediated induction of TCR mRNA is both rapid and reversible, it is unlikely that new DNA rearrangements are responsible for the induction [29].

Gene context of Gene Rearrangement

• In scid mice, antigen receptor gene rearrangements are initiated normally, but impaired joining of coding ends prevents assembly of functional receptor genes, resulting in arrest of B- and T-cell development [30].
• Unexpectedly, both mutant alleles are shown to contain DNA rearrangements, located > 100 kb 5' of Mgf-coding sequences, that lead to tissue-specific effects on Mgf mRNA expression [31].
• A neutralizing monoclonal antibody against Shh increases differentiation of DN to DP thymocytes, and Shh protein arrests thymocyte differentiation at the CD25+ DN stage, after T cell receptor beta (TCRbeta) gene rearrangement [32].
• Regulation of interleukin 7-dependent immunoglobulin heavy-chain variable gene rearrangements by transcription factor STAT5 [33].
• Moreover, our results demonstrate that expression of Pax5 in early thymocytes is sufficient to induce VH to DJH rearrangements in CD4+CD8+ T cells and lead us to suggest that Pax5 may play a direct role in the lineage-specific regulation of immunoglobulin heavy chain gene rearrangement [34].

Analytical, diagnostic and therapeutic context of Gene Rearrangement

• Southern blot analysis for genomic Ig H chain gene rearrangements was done to fully assess the extent of clonal heterogeneity among multiple mu kappa+ XLA B cell lines derived from two patients; all the B cell lines possessed distinct gene rearrangement patterns demonstrating their clonal unrelatedness [35].
• Gene targeting in the Ig kappa locus: efficient generation of lambda chain-expressing B cells, independent of gene rearrangements in Ig kappa [36].
• Somatic mutations and intraclonal diversity in the VH genes indicate a germinal center B-cell origin of the HRS cells in a case of lymphocyte-predominant HD, whereas in a case of mixed-cellularity HD the sequence analysis revealed only nonfunctional V gene rearrangements, suggesting a pre-B-cell origin [37].
• Infant acute lymphoblastic leukemia (ALL) with MLL gene rearrangements is characterized by early pre-B phenotype (CD10(-)/CD19(+)) and poor treatment outcome [38].
• We studied BCL6 gene rearrangement by the methodology of long-distance inverse polymerase chain reaction (LDI-PCR) [39].

References