Study of minimal residual disease in B-cell lineage acute lymphoblastic leukemia of childhood, using clone-specific...

In B-cell lineage acute lymphoblastic leukemia (B-ALL), the clonal rearrangements of the immunoglobulin heavy chain gene locus (IgH), can be used as a molecular marker for the detection of minimal residual disease (MRD). Patients in complete remission may still harbor leukemic cells undetectable by conventional methods such as light-microscopic examination, immunophenotyping and cytogenetics. 30 children with B-ALL were screened at diagnosis by polymerase chain reaction (PCR) for their IgH gene repertoire. 7/30 patients were extensively studied using patient-specific oligonucleotide probes derived from the sequence analysis of bone marrow (BM) samples at diagnosis. 210 PCR products from follow-up BM samples corresponding to these 7 patients were hybridized with the appropriate clone-specific probe in order to detect MRD with high sensitivity and specificity. All the patients were in morphological remission during and after therapy. 25/30 patients were PCR positive at diagnosis. 4/7 patients who were examined for MRD had detectable disease in various periods after diagnosis. Molecular signs of residual cells can persist for a long time during and after therapy. Long term follow-up of MRD could determine the period of therapy and predict relapse, indicating therapeutic interventions.