Prediction of immunophenotype, treatment response, and relapse in childhood acute lymphoblastic leukemia using DNA microarrays

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Abstract
Gene expression profiling is a promising tool for classification of pediatric acute lymphoblastic leukemia (ALL). We analyzed the gene expression at the time of diagnosis for 45 Danish children with ALL. The prediction of 5-year event-free survival or relapse after treatment by NOPHO-ALL92 or 2000 protocols resulted in a classification accuracy of 78% and a Matthew's correlation coefficient of 0.59 independently of immunophenotypes. The sensitivity and specificity for prediction of relapse were 87% and 69% respectively. Prediction of high vs low levels of the minimal residual disease (MRD) on day 29 (0.1% or 0.01%) resulted in an accuracy of 100% for precursor-B samples. The classification accuracy of precursor-B- vs T-lineage immunophenotypes was 100% even in samples with as little as 10% leukemic blast cells, and the immunophenotype classifier constructed in this study was able to classify 131 of 132 samples from a previous study correctly. Our study indicates that the Affymetrix Focus Array GeneChip may be used without loss of classification performance compared to previous studies using the far more extensive U133A+B GeneChip set. Further studies should focus on prediction of MRD, as this prediction would relate strongly to long-term outcome and could thus determine the intensity of induction therapy.