PCR–heteroduplex analysis of TCR γ, δ 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) γ and δ gene rearrangements in 24 T-ALL patients at diagnosis. 52.4% revealed Vδ1-Jδ1; 48% Vδ2-Dδ3; 62.5% Vγ1-Jγ1 and 46% both Vδ1-Jδ1 and Vγ1-Jγ1 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.