The use of DNA probes to monitor minimal residual disease in childhood acute lymphoblastic leukaemia

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Abstract
DNA probes to both the joining region (JH) of the immunoglobulin heavy chain gene (IgH) and to the β chain of the T-cell antigen receptor complex (TCR) have been used as tumour-specific markers to monitor the rearrangements of the IgH chain gene and the TCR β gene in the blast cells of children presenting with acute lymphoblastic leukaemia (ALL) of B or T cell origin. Blast cells from 68 children with early B cell ALL and eight with T-ALL were examined at presentation, at day 28 after commencement of therapy and at varying times thereafter. An additional 43 patients (42 with B cell ALL, one with T-ALL) were studied both at presentation, at completion of their 2-year treatment course and 3 months later. Twelve patients, drawn from both these groups, were studied at relapse as were a further eight patients in whom an extramedullary relapse had occurred. Persistence of clonally-derived cells as a predictor of early relapse was seen in the day 28 bone marrows of 11/76 newly-diagnosed children (nine early B and two T-ALL) followed by rapid, overt relapse in four of the early B ALL cases. No minimal residual disease (MRD) was detected in bone marrows from any of the 43 patients completing their 2-year treatment course, but six of these subsequently relapsed at varying time periods thereafter. Identical patterns of rearrangement at both presentation and relapse were seen in most cases. Oligoclonality, or multiple IgH chain gene rearrangements was seen in the blast cells of 15% of patients with early B cell ALL. No correlation between oligoclonality, high white count, unfavourable phenotype, or abnormal karyotype could, however, be ascertained.