title: PCR-heteroduplex analysis of TCR gamma, delta and TAL-1 deletions in T-acute lymphoblastic leukemias: implications in the detection of minimal residual disease.
abstract: Detection of MRD remains one of the major goals in the treatment of acute lymphoblastic leukemia (ALL). We have used the polymerase chain reaction (PCR)-heteroduplex (HD) analysis to assess and confirm the clonal expansion of T cell receptor (TCR) gamma and delta gene rearrangements in 24 T-ALL patients at diagnosis. 52.4% revealed Vdelta1-Jdelta1; 48% Vdelta2-Ddelta3; 62.5% Vgamma1-Jgamma1 and 46% both Vdelta1-Jdelta1 and Vgamma1-Jgamma1 clonal rearrangements. 6/24 patients had TAL-1 deletion. These clonal markers were used to monitor MRD in remission/relapse bone marrow samples for periods ranging from 6 to 75 months after diagnosis. Patients who relapsed and died revealed a continuous PCR-HD positivity in their clinical remission bone marrow samples. HD analysis established identical diagnostic clone at relapse. Patients who are in long-term clinical and morphological remission achieved PCR-HD negativity in their 8-12 months bone marrow remission samples and continue to be PCR-HD negative. MRD monitored in six patients with two diagnostic PCR--HD positive clonal markers reveal an identical pattern ensuring circumvention of false positive and negative results. Thus, we conclude that PCR followed by HD analysis is a useful technique to monitor MRD in remission/relapse samples in ALL patients.
authors.affiliation: Cancer Institute (WIA), Sardar Patel Road, Guindy, Chennai, Tamil Nadu, India. caninst@md2.vsnl.net.in
authors.forename: K
authors.initials: K
authors.lastname: Nirmala
authors.forename: K R
authors.initials: KR
authors.lastname: Rajalekshmy
authors.forename: S G
authors.initials: SG
authors.lastname: Raman
authors.forename: V
authors.initials: V
authors.lastname: Shanta
authors.forename: T
authors.initials: T
authors.lastname: Rajkumar
mesh_terms: D000293:Adolescent; D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins; D002648:Child; D002675:Child, Preschool; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor / Q000235:genetics*; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor / Q000235:genetics*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D018365:Neoplasm, Residual; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011518:Proto-Oncogene Proteins; D012008:Recurrence; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D014157:Transcription Factors; C067143:TAL1 protein, human