PCR–heteroduplex analysis of TCR γ, δ and TAL-1 deletions in T-acute lymphoblastic leukemias: implications in the detection of minimal residual disease

Nirmala, K.; Rajalekshmy, Kamalalayam Raghavan; Raman, Swaminathan Ganapathi; Shanta, V.; Rajkumar, Thangarajan

doi:10.1016/s0145-2126(01)00130-8

Cited by 9 publications

(7 citation statements)

References 34 publications

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“…DNA was isolated from the MNC using QIAamp kit (Qiagen, Hilden, Germany) and quantitated by Gene Quant (Amersham); the quality was checked by amplifying for the c-abl gene [5].…”

Section: Dna Isolation From Mncmentioning

confidence: 99%

“…Although 60-70% of the patients achieve remission, later on 30-40% of the patients relapse due to the persistence of clonogenic residual leukemic cells during treatment. Clonal markers identified at diagnosis are used as targets for monitoring and quantitating the minimal residual disease (MRD) [5][6][7] and can provide prognostic information of the patients [8]. There is a paucity of information available on the frequency of T-cell receptor gamma and delta (TCRG) and (TCRD) gene rearrangements and its junctional region characteristics in South Indian T-ALL patients.…”

Section: Introductionmentioning

confidence: 99%

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T‐cell receptor gamma and delta gene rearrangements and junctional region characteristics in south Indian patients with T‐cell acute lymphoblastic leukemia

et al. 2006

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Clonal T-cell receptor (TCR) gamma and delta gene rearrangements were studied in 40 T-ALL cases (pediatrics, 29; adults, 11) using PCR with homo-heteroduplex analysis. At least one clonal TCRG or TCRD rearrangement was detected in 34 (85%) cases. TCR gamma (TCRG) rearrangement was detected in 25 (62.5%) cases that included 16 (55%) pediatrics and 9 (81.8%) adults. TCR delta (TCRD) rearrangement was detected in 14/40 (35%) cases, which included 12 (41%) pediatrics and 2 (18%) adults. The frequency of VgI-Jg1.3/2.3 was significantly more in adults than pediatrics (81.8% vs. 41.3%, P = 0.02). In TCRD, Vd1-Jd1 was rearranged in 10 (25%) cases. The surface membrane CD3 positive cases are significantly associated with absence of TCRD rearrangements (surface membrane CD3+ TCRd-84% vs. surface membrane CD3-TCRd-48%, P value = 0.03). Junctional region sequence analyzed with 10 cases each, of TCRG and TCRD, revealed an average junctional region of 7.4 nucleotides (range 2-18 nucleotides) in TCRG and 27 nucleotides (range 14-42 nucleotides) in TCRDcomplete rearrangements. In TCRG, trimming at the ends of Vg and Jg germline nucleotides resulted in deletion, on an average of 9.2 nucleotides. In TCRD, deletion of nucleotides of the Vd and Jd gene segments on an average was 3.5 nucleotides. The junctional region of TCRD is more diverse than TCRG; nevertheless, the frequency of TCRG was more than that of TCRD and hence we rely more on TCRG clonal markers to quantitate the minimal residual disease in T-ALL. Am. J. Hematol. 82:215-221, 2007. V V C 2006 Wiley-Liss, Inc.

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“…DNA was isolated from the MNC using QIAamp kit (Qiagen, Hilden, Germany) and quantitated by Gene Quant (Amersham); the quality was checked by amplifying for the c-abl gene [5].…”

Section: Dna Isolation From Mncmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

T‐cell receptor gamma and delta gene rearrangements and junctional region characteristics in south Indian patients with T‐cell acute lymphoblastic leukemia

et al. 2006

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“…[10][11][12][13][14][15][16] So far, mainly clonal T-cell receptor gamma (TCRG) and delta (TCRD) gene rearrangements as well as SIL-TAL1 fusion genes have been used as PCR tools for MRD quantification in T-ALL. [1][2][3]8,[17][18][19][20][21] However, the SIL-TAL1 fusion genes are detected in only 5-25% of T-ALL patients, 1,22 and also clonal TCRD gene rearrangements are found in just about 50% of patients. 23,24 In addition, crosslineage immunoglobulin heavy-chain rearrangements can serve as clonal markers in T-ALL, but they are also relatively rare.…”

Section: Introductionmentioning

confidence: 99%

Rearranged T-cell receptor beta genes represent powerful targets for quantification of minimal residual disease in childhood and adult T-cell acute lymphoblastic leukemia

et al. 2004

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Current MRD studies in T-cell acute lymphoblastic leukemia (T-ALL) mainly use T-cell receptor gamma, delta and SIL-TAL1 gene rearrangements as MRD-PCR targets. However, low frequency or limited diversity of these markers restricts the number of evaluable patients, particularly because two markers are recommended for MRD monitoring. Hence, we developed a new strategy implementing the TCR beta (TCRB) locus for MRD quantification. The frequency and characteristics of complete and incomplete TCRB rearrangements were investigated in 53 childhood and 100 adult T-ALL patients using the BIOMED-2 multiplex PCR assay. Clonal rearrangements were identified in 92% both childhood and adult T-ALL (Vb-Db-Jb rearrangements in 80%, Db-Jb rearrangements in 53%). Comparative sequence analysis of 203 TCRB recombinations revealed preferential usage of the 'end-stage' segment Jb2.7 in childhood T-ALL (27%), whereas Jb2.3 was most frequently involved in adult T-ALL (24%). In complete rearrangements, three downstream Vb segments (19-1/20-1/21-1) were preferentially used. Subsequently, a TCRB real-time quantitative PCR assay to quantify MRD with 13 germline Jb primer/probe combinations and allele-specific oligonucleotides was developed and applied to 60 clonal TCRB rearrangements. The assay allowed the detection of one leukemic cell within at least 10 4 polyclonal cells in 93% of cases and will be of high value for future MRD studies.

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“…Because most of the patients with morphologic remission have residual disease not indicated by morphological analysis, the importance and high prognostic value of MRD monitoring and follow-up are demonstrated in these patients (Campana 2009b;Szczepański et al 2002c). At least 20 % of the patients experience disease recurrence, and severity of treatment raises the risk of secondary malignancies, which shows the importance of specific and sensitive molecular techniques (Flohr et al 2008b;Nirmala et al 2002). Factors such as gender, age and white blood cell (WBC) count at diagnosis, immunophenotype, and chromosomal aberrations are significant in predicting disease relapse (Schrappe et al 2000).…”

Section: Tcr Gene Rearrangement For Mrd Monitoringmentioning

confidence: 99%

“…1) (Van der Velden et al 2003b;Bassan et al 2009). According to the frequency of TCR γ/δ in both ALL types (more than 90 % of type T and over 55 % in B-lineage), low oligoclonality, and easy detection, rearrangements of these genes are easier to detect by PCR assays (Szczepanski et al 2000a;Brumpt et al 2000;Nirmala et al 2002). Due to the immense size difference between alpha and beta gene segments and the stability of gamma and delta genes at diagnosis and relapse, the latter genes are better markers to evaluate (Table 1) (Szczepański et al 2002a;Brüggemann et al 2004;Martinelli et al 1997).…”

Section: Tcr Gene Rearrangement For Mrd Monitoringmentioning

confidence: 99%

Prognostic value and clinical significance of TCR rearrangements for MRD monitoring in ALL patients

et al. 2015

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Acute lymphoblastic leukemia is a hematological malignancy of lymphoid progenitor cells associated with excessive proliferation of lymphocytes, and lymphocyte markers can be used for the diagnosis and assessment of disease. Cell surface receptors, including T cell receptor and immunoglobulin (on T and B cells, respectively), are among the most important lymphocyte markers. Gene segment variation, i.e., involvement of several genes in the expression of each receptor, is effective on extensive rearrangement of cell surface receptors. These receptors can be observed in both T-acute lymphoblastic leukemia (ALL) and precursor B-ALL cells. In this study, we have discussed T cell receptor (TCR) gene rearrangements in ALL. As leukemia cell proliferation originates from a unique clone, clone-specific rearrangement can be very helpful in diagnosis and detection of remaining malignant cells from among normal cells for minimal residual disease. On the other hand, each of the TCR genes is associated with translocation in ALL types, and the result of gene rearrangements can be used as prognosis markers.

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PCR–heteroduplex analysis of TCR γ, δ and TAL-1 deletions in T-acute lymphoblastic leukemias: implications in the detection of minimal residual disease

Cited by 9 publications

References 34 publications

T‐cell receptor gamma and delta gene rearrangements and junctional region characteristics in south Indian patients with T‐cell acute lymphoblastic leukemia

T‐cell receptor gamma and delta gene rearrangements and junctional region characteristics in south Indian patients with T‐cell acute lymphoblastic leukemia

Rearranged T-cell receptor beta genes represent powerful targets for quantification of minimal residual disease in childhood and adult T-cell acute lymphoblastic leukemia

Prognostic value and clinical significance of TCR rearrangements for MRD monitoring in ALL patients

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