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

A translocation between chromosomes 7 and 9, t(7;9), has been described in cell lines derived from the malignant cells of children with acute T-cell lymphoblastic leukemia or lymphoma. Our cytogenetic analysis of one such cell line, SUP-T3, demonstrates that the breakpoints on chromosomes 7 and 9 lie within bands q36 and q34, respectively, corresponding to the location of the gene encoding the beta chain of the T-cell receptor, TCRB, and the gene homologous to the transforming gene of the Abelson murine leukemia virus, ABL. We investigated the role of these genes in the t(7;9). In situ chromosomal hybridization of TCRB and ABL probes to metaphase cells from SUP-T3 demonstrated that ABL is translocated from chromosome 9 to 7 and that all or part of TCRB is translocated from chromosome 7 to 9. Southern blot analysis revealed that both TCRB alleles were rearranged; however, it could not be determined whether the translocation breakpoint lies within this gene. Pulsed-field gel electrophoresis and Southern blot analysis were used to examine more than 500 kilobases of the ABL locus; we concluded that there are no rearrangements within 250 kb in either direction of the sequences homologous to v-abl. Additionally, no abnormal ABL protein was detected in an in vitro phosphorylation assay. These results indicate that, in SUP-T3, the breakpoint on chromosome 9 lies proximal to ABL and that the break results in no apparent alteration of the ABL protein. We therefore hypothesize that another gene on chromosome 9, at band q34, plays a role in this translocation. This study also demonstrates that pulsed-field gel electrophoresis is a powerful new tool for the analysis of human chromosomal translocations.
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PMID:Molecular analysis of TCRB and ABL in a t(7;9)-containing cell line (SUP-T3) from a human T-cell leukemia. 302 59

The use of probes to genes (IG and TCRB) encoding immunoglobulins (IG) and the beta chain of the T-cell antigen receptor (TCRB), respectively, have become a sensitive means to assess clonality and lineage in lymphoid malignancies. It has become apparent that some individual cases show rearrangements of both IG and TCRB genes. In an attempt to more accurately define cell lineage we have analyzed cells from patients with B- or T-cell leukemia (n = 26) at various stages of maturation with probes to two additional TCR genes, TCRG and TCRA (encoding the TCR gamma and alpha chains, respectively), as well as the IG heavy chain joining region (IGHJ) and TCRB genes. On Southern blot analysis, the mature T-cell leukemia cells studied had rearranged TCRG and TCRB while IGHJ remained as in the germ line. The mature B-cell leukemia cells studied had rearranged IGHJ with germ-line TCRG and TCRB. These data suggest that, in the majority of more mature leukemias, cells have rearranged IG or TCR genes but not both. In contrast, cells from five of nine precursor B-cell leukemia patients and cell lines from one of four precursor T-cell leukemia patients had rearranged both IGHJ and TCR genes. TCRG and TCRB mRNAs were expressed in the cells of precursor T- but not B-cell leukemia patients studied. The spectrum of leukemia cells studied within the T-cell series permitted an assessment of the order of TCR gene rearrangements. Two of 13 patients had cells with germ-line TCRG and TCRB, 2 patients had cells with rearranged TCRG alone, and the remainder had cells with rearranged TCRG and TCRB. TCRG and TCRB mRNAs were expressed in precursor T-cell leukemia cells, whereas TCRB and TCRA were expressed in mature T-cell leukemia cells. These results parallel observations from mouse studies on gene expression and support the view of a hierarchy of TCR gene rearrangements in T-lymphocyte ontogeny. TCRG genes are rearranged first, subsequently TCRB genes are rearranged, followed by TCRA gene activation.
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PMID:Immunoglobulin and T-cell receptor gene rearrangement and expression in human lymphoid leukemia cells at different stages of maturation. 346 80

The presence of Ig and TCR gene rearrangement has been reported to occur in ANLL. However, most of the studies have been performed in short series of patients and, in general, not all rearranging genes have been included. We have investigated the configuration of immunoglobulin (Ig) and T-cell receptor loci (TCR) in a series of 160 untreated patients with de novo acute non-lymphoblastic leukaemia (ANLL) and correlated the results with the morphological and immunophenotypic characteristics of blast cells. IGH gene rearrangement was detected in 16/160 cases analysed (10%) and IGK was rearranged in half of them. The incidence of cases displaying TCRB, TCRG and TCRD rearrangements was 5.6%, 13.8% and 13%, respectively. Concomitant recombinatorial events including different Ig and/or TCR genes were frequently detected. Gene rearrangement was not related to the stage of cell differentiation within the myeloid lineage assessed both by morphological and immunophenotypic criteria. Regarding the correlation with the presence of lymphoid related markers, the only relevant association was between the expression of CD7 antigen and TCRG and TCRD gene rearrangement. Our results show that the incidence of gene rearrangement in ANLL may be slightly higher than previously suspected, and that it is not associated with early stages of cell differentiation nor to the expression of lymphoid markers.
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PMID:Gene rearrangement in acute non-lymphoblastic leukaemia: correlation with morphological and immunophenotypic characteristics of blast cells. 753 Apr 75

We report two cases of acute lymphoblastic leukemia (ALL) with a late-appearing Philadelphia chromosome (Ph1), confirmed by the expression of BCR-ABL mRNA, using the reverse transcriptase/polymerase chain reaction (RT/PCR) technique. The first patient was a 10-year-old boy with precursor B cell type ALL-L1 (FAB classification). At diagnosis, no metaphase cells were found by chromosome analysis and BCR-ABL mRNA was not observed. At the beginning of relapse, which occurred after 7 months of complete remission, a normal karyotype was observed. At the terminal stage, leukemic cells with Ph1 and BCR-ABL mRNA for the P190 variety were observed. The second patient was a 12-year-old boy with immature T cell type ALL-L1. The metaphase cells showed a 9p- chromosome at diagnosis and Ph1 appeared in addition to 9p- at relapse. Hybrid mRNA for the P210 variety was detected only when Ph1 had developed. The blast cells with Ph1 were derived from the original leukemic clone through clonal evolution, since the same clonal rearrangements of IGH or TCRB were detected in leukemic cells obtained both at diagnosis and relapse in both patients. Thus, in both cases, Ph1 was detected only in the course of ALL along with expression of BCR-ABL mRNA. This observation also confirmed that, as in de novo Ph1-positive ALL, both the P190 and P210 varieties of BCR-ABL mRNA are observed in ALL with late-appearing Ph1.
Leukemia 1995 Oct
PMID:A late-appearing Philadelphia chromosome in acute lymphoblastic leukemia confirmed by expression of BCR-ABL mRNA. 756 11

Molecular analysis of T cell receptor (TCR) genes is frequently used to prove or exclude clonality and thereby support the diagnosis of suspect T cell proliferations. PCR techniques are more and more being used for molecular clonality studies. The main disadvantage of the PCR-based detection of clonal TCR gene rearrangements, is the risk of false-positive results due to 'background' amplification of similar rearrangements in polyclonal reactive T lymphocytes. Therefore, PCR-based clonality assessment should include analyses that discern between PCR products derived from monoclonal and polyclonal cell populations. One such method is heteroduplex analysis, in which homo- and heteroduplexes resulting from denaturation (at 94 degrees C) and renaturation (at lower temperatures) of PCR products, are separated in non-denaturing polyacrylamide gels based on their conformation. After denaturation/renaturation, PCR products of clonally rearranged TCR genes give rise to homoduplexes, whereas in case of polyclonal cells heteroduplexes with heterogeneous junctions are formed. We studied heteroduplex PCR analysis of TCR gene rearrangements with respect to the time and temperature of renaturation and the size of the PCR products. Variation in time did not have much influence, but higher renaturation temperatures (>30 degrees C) clearly showed better duplex formation. Nevertheless, distinction between monoclonal and polyclonal samples was found to be more reliable at a renaturation temperature of 4 degrees C, using relatively short PCR products. 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). Clonal TCRB and TCRD gene rearrangements could be detected with a sensitivity of at least 5%, whereas the sensitivity for TCRG genes was somewhat lower (10-15%). The latter could be improved by use of Vgamma member primers instead of Vgamma family primers. We conclude from our results that heteroduplex PCR analysis of TCR gene rearrangements is a simple, rapid and cheap alternative to Southern blot analysis for detection of clonally rearranged TCR genes.
Leukemia 1997 Dec
PMID:Heteroduplex PCR analysis of rearranged T cell receptor genes for clonality assessment in suspect T cell proliferations. 944 40

We report a case of large granular lymphocytic leukaemia (LGLL) with mixed T-cell/B-cell phenotypes. The LGLL cells expressed T-cell markers such as CD1, CD2, CD3, CD5, CD7, CD8 and CD57. The CD8+ LGLL cells coexpressed B-cell markers including CD20 and PCA-1, and a fraction of purified CD8+ LGLL cells secreted double isotypes of immunoglobulins (IgG-kappa and IgA-kappa). Both TCRB and IGH genes were clonally rearranged. The LGLL cells could be divided into at least three subpopulations that were cytogenetically distinct, and all subpopulations involved the 11q23. The expression of both T- and B-cell markers on the LGLL cells suggests the involvement of a putative common lymphoid progenitor in leukaemic transformation.
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PMID:Large granular lymphocytic leukaemia with a mixed T-cell/B-cell phenotype. 948 15

In order to gain insight into immunoglobulin (Ig) and T cell receptor (TCR) gene rearrangements in adult acute lymphoblastic leukemia (ALL), we studied 48 adult patients: 26 with precursor-B-ALL and 22 with T-ALL. Southern blotting (SB) with multiple DNA probes for the IGH, IGK, TCRB, TCRG, TCRD and TAL1 loci revealed rearrangement patterns largely comparable to pediatric ALL, but several differences were found for precursor-B-ALL patients. Firstly, adult patients showed a lower level of oligoclonality in the IGH gene locus (five out of 26 patients; 19%) despite a comparable incidence of IGH gene rearrangements (24 out of 26 patients; 92%). Secondly, all detected IGK gene deletions (n = 12) concerned rearrangements of the kappa deleting element (Kde) to Vkappa gene segments, which represent two-thirds of the Kde rearrangements in pediatric precursor-B-ALL and only half of the Kde rearrangements in mature B cell leukemias. Thirdly, a striking predominance of immature Ddelta2-Ddelta3 cross-lineage recombinations was observed (seven out of 16 TCRD rearrangements; 44%), whereas more mature Vdelta2-Ddelta3 gene rearrangements occurred less frequently (six out of 16 TCRD rearrangements; 38% vs >70% in pediatric precursor-B-ALL). Together these data suggest that the Ig/TCR genotype of precursor-B-ALL is more immature and more stable in adults than in children. We also evaluated whether heteroduplex analysis of polymerase chain reaction (PCR) products of rearranged Ig and TCR genes can be used for identification of molecular targets for minimal residual disease (MRD) detection. Using five of the major gene targets (IGH, IGK, TCRG, TCRD and TAL1 deletion), we compared the SB data and heteroduplex PCR results. High concordance between the two methods ranging from 96 to 100% was found for IGK, TCRG and TAL1 genes. The concordance was lower for IGH (70%) and TCRD genes (90%), which may be explained by incomplete or 'atypical' rearrangements or by translocations detectable only by SB. Finally, the heteroduplex PCR data indicate, that MRD monitoring is possible in almost 90% of adult precursor-B-ALL and >95% of adult T-ALL patients.
Leukemia 1998 Jul
PMID:Immunoglobulin and T cell receptor gene rearrangement patterns in acute lymphoblastic leukemia are less mature in adults than in children: implications for selection of PCR targets for detection of minimal residual disease. 966 94

A large series of 202 childhood precursor-B cell acute lymphoblastic leukemia (ALL) patients was analyzed by Southern blotting (SB) for cross-lineage rearrangements and/or deletions in the T cell receptor TCRB, TCRG and TCRD loci. In 93% (187/201) of the precursor-B-ALL patients one or more genes were rearranged and/or deleted. TCRB gene rearrangements were found in 35% (69/196), TCRG gene rearrangements in 59% (113/192), TCRD gene rearrangements in 55% (112/202), and isolated monoallelic or biallelic deletions of TCRD loci in 34% (68/202) of the cases. TCRB gene rearrangements involved exclusively the Jbeta2 locus with complete V(D)Jbeta2 joinings in 53% of gene rearrangements and incomplete Dbeta-Jbeta2 gene rearrangements in 33%. TCRG gene rearrangements frequently occurred on both alleles (65% of cases) and in approximately 70% concerned rearrangements to Jgamma1 gene segments. Most rearranged TCRD alleles (80%) represented incomplete Vdelta2-Ddelta3 or Ddelta2-Ddelta3 gene rearrangements, while the remaining TCRD gene rearrangements remained unidentified. 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). The concordance between SB and heteroduplex PCR analysis for detection of the various types of clonal TCRG and TCRD gene rearrangements ranged between 78% and 87%. The discrepancies could be assigned to the presence of 'atypical' TCRD gene rearrangements or translocations only detectable by SB, but also to efficient PCR-based detection of rearrangements derived from small subclones, which are difficult to detect with SB. Indications for oligoclonality were observed in 38% and 30% of patients with TCRG and TCRD gene rearrangements, respectively, which is comparable to the frequency of oligoclonality in IGH locus. Based on the combined data it was possible to reduce the broad panel of six TCRD and 12 TCRG primer combinations for MRD studies to two TCRD combinations (Vdelta2-Ddelta3 and Ddelta2-Ddelta3) and six TCRG combinations (VgammaI, VgammaII, VgammaIV family-specific primers with Jgamma1.1/2.1 and Jgamma1.3/2.3 primers) resulting in the detection of 80% and 97% of all TCRD and TCRG gene rearrangements, respectively. Finally, the heteroduplex PCR data indicate that MRD monitoring with TCRG and/or TCRD targets is possible in approximately 80% of childhood precursor-B-ALL patients; approximately 55% of patients even have two TCRG and/or TCRD targets.
Leukemia 1999 Feb
PMID:Cross-lineage T cell receptor gene rearrangements occur in more than ninety percent of childhood precursor-B acute lymphoblastic leukemias: alternative PCR targets for detection of minimal residual disease. 1002 93

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. In 15 cases membrane expression of TCRgammadelta proteins could be studied extensively by flow cytometry with a new Vgamma/Vdelta antibody panel. Virtually all TCRgammadelta+ T-ALLs expressed TdT, CD2, CD3, CD5, CD6, and CD7, but they were heterogeneous in their CD1/CD4/CD8 immunophenotype. The majority expressed either CD4+/CD8- or CD4+/CD8+, whereas only 7/30 TCRgammadelta+ T-ALLs lacked both antigens. Despite heterogeneity in the rearranged TCRG and TCRD genes, we found preferential protein expression of VgammaI (21/30), Jgamma2.3 (19/30) and Cgamma2 (21/30) gene products in the TCRgammadelta+ T-ALL. Expressed TCRD genes were largely limited to Vdelta1-Jdelta1, except for six patients who expressed non-Vdelta1 TCRdelta chains (Vdelta2-Jdelta1, Vdelta2-Jdelta3, Vdelta3-Jdelta1, Vdelta6-Jdelta2, and two Valpha-Jdelta1). In spite of the relatively limited combinatorial repertoire of the TCRG and TCRD genes, the junctional region diversity of the expressed genes was extensive. The Vgamma/Vdelta antibody panel confirmed the predominant, but not exclusive, expression of VgammaI and Vdelta1 proteins. Importantly, not a single T-ALL expressed the common peripheral blood Vgamma9+/Vdelta2+ phenotype. These immunogenotypic and immunophenotypic characteristics represent excellent targets for flow cytometric and PCR-based detection of 'minimal residual disease' in all TCRgammadelta+ T-ALL. Comparison of non-Vdelta1+ TCRgammadelta T-ALLs with the more common Vdelta1+ type showed a trend towards a more mature immunogenotype in the former. Firstly, more complete TCRD rearrangements were identified on the non-expressed allele in the non-Vdelta1+ group (83% vs 43%); secondly, a higher frequency of 'end-stage' Jgamma2.3 gene rearrangements was found in non-Vdelta1 cases on both TCRG alleles (83% vs 66%); thirdly, a higher frequency of complete TCRB rearrangements was found in non-Vdelta1 cases (79% vs 50%).
Leukemia 1999 Feb
PMID:Immunophenotypic and immunogenotypic characteristics of TCRgammadelta+ T cell acute lymphoblastic leukemia. 1002 94

Chromosomal aberrations with breakpoints in T-cell receptor (TCR) gene loci are recurrent in several T-cell malignancies. Although the importance of interphase cytogenetics has been extensively shown in B-cell lymphomas, hardly any molecular cytogenetic tools are available for recurrent changes in T-cell disorders. Thus, we have established fluorescence in situ hybridization (FISH)-based break-apart assays for the TCRA/D (14q11), TCRB (7q34) and TCRG (7p14) genes and the TCL cluster (14q32). The assays were validated in normal controls as well as in 43 T-cell malignancies with cytogenetically proven 14q11, 7q34-35 or 7p13-21 aberrations. Breakpoints in TCRA/D, TCRB and TCRG could be diagnosed by these assays in 32/33 T-cell neoplasms with chromosome 14q11, 3/6 with 7q34-35 and 1/7 with 7p13-21 alterations, respectively. 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. 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. These new FISH and FICTION assays provide sensitive, rapid and accurate tools for the diagnosis and biological characterization of T-cell malignancies.
Leukemia 2003 Apr
PMID:Molecular cytogenetic detection of chromosomal breakpoints in T-cell receptor gene loci. 1268 31


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