[Dynamic monitoring of minimal residual disease in acute lymphoid leukemia].


    The aim of this study was to establish a method for quantitative detection of immunoglobulin heavy chain (IgH) gene rearrangements and to explore its clinical application in monitoring minimal residual disease (MRD) of acute lymphoid leukemia (ALL). Clonal IgH gene rearrangements in 51 patients with ALL at diagnosis were identified by multiplex PCR assay. PCR products were sequenced and pairwised in IMGT data base. Allele-specific oligonucleotides primers were designed complementary to the junctional region. The conservative JH primers combined with TaqMan probes were used to monitor the level of MRD in ALL patients. The sensitivity and specificity were assessed as well. The results indicated that out of all the 51 ALL patients, IgH rearrangements were identified in 21 cases, and 15 patients out of them were quantified. The slope of the standard curves was -3.1 to -3.9 and the correlation coefficients of all standard curves were > 0.98. The sensitivity was between 10(-4) and 10(-5), only one patient's sensitivity was 10(-3). Most of the quantitative range was less than 10(-4). The background's nonspecific amplification was detectable at a low level and had a little influence on results. 7 patients whose MRD level below 10(-3) kept complete remission and another 8 patients whose MRD level above 10(-3) had a higher relapse rate. It is concluded that the analysis of IgH gene rearrangements with RQ-PCR is a highly sensitive, specific and reliable method for accurate evaluation of MRD in ALL. The data indicates a high correlation between the level of IgH rearrangments and the prognosis in ALL patients.