Prediction of immunophenotype, treatment response, and relapse in childhood acute lymphoblastic leukemia using DNA microarrays.
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.
Willenbrock
H
H
Center for Biological Sequence Analysis, Technical University of Denmark, Lyngby, Denmark.
Juncker
A S
AS
Schmiegelow
K
K
Knudsen
S
S
Ryder
L P
LP
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D016000:Cluster Analysis; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling / Q000706:statistics & numerical data*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D008297:Male; D018365:Neoplasm, Residual; D020411:Oligonucleotide Array Sequence Analysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D011237:Predictive Value of Tests; D011379:Prognosis; D012008:Recurrence; D012680:Sensitivity and Specificity; D016896:Treatment Outcome