CHARACTERIZATION OF NON-CONCORDANCE IN THE T-CELL RECEPTOR-GAMMA CHAIN GENES AT PRESENTATION AND CLINICAL RELAPSE IN ACUTE LYMPHOBLASTIC-LEUKEMIA

We have analysed the structure of the T-cell receptor gamma chain (TCR G) genes in a panel of biopsies taken from 24 patients with acute lymp hoblastic leukemia (ALL) (13 cALL, one pre-B ALL, two null ALL and eig ht T-ALL) at presentation and at clinical relapse. In the majority of cases (18/24) the structure of these genes was concordant, but in a si gnificant minority of cases (6/24) the TCRG genes were in a different conformation at different clinical stages. In three of these patients (one null ALL, two T-ALL) the clonal TCRG rearrangements detected at p resentation were absent at relapse possibly as a result of clonal regr ession. In one other patient (cALL), the TCRG locus at relapse was rea rranged to V genes which are located downstream of the V genes found i n the presentation rearrangement. This indicates that the relapse leuk emic clone is probably the result of clonal evolution. In two patients (one cALL, one T-ALL) there were no clonally dominant rearrangements of the TCRG genes at presentation, but evidence for clonal rearrangeme nts at relapse, possibly as a result of clonal progression. The struct ure of the IgH genes were determined in four of the six patients with clonal changes in the TCRG genes and were found to be concordant. The changes in TCRG gene structure were not restricted to ALL of any one p articular age group, phenotype or duration of first remission. These d ata indicate that the assignment of clonal specific markers based upon the sequence of TCRG rearrangements at presentation may not always be useful in the detection of minimal residual disease in ALL.