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

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 (X0.1% or p0.01%) resulted in an accuracy of 100% for precursor-B samples. The classification accuracy of precursor-B-vs Tlineage 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 þ 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.

Distinct gene expression profiles determine molecular treatment response in childhood acute lymphoblastic leukemia

“…by guest www.bloodjournal.org From our data with published data analyzing gene expression profiles of patients with relapsed and successfully treated ALL and treatment-resistant compared with sensitive ALL, respectively. [11][12][13][14][15] A remarkable concordance could be observed comparing our results with the data recently published by Chiaretti et al, 15 who analyzed the expression signatures of adult T-cell ALL. Chiaretti et al 15 identified a set of only 3 genes that were predictive of duration of remission and a list of 30 genes expressed at low levels in treatment-resistant T-cell ALL.…”

The expression of 70 apoptosis genes in relation to lineage, genetic subtype, cellular drug resistance, and outcome in childhood acute lymphoblastic leukemia

“…This notion is supported by the absence of apoptosis genes among the genes previously associated with treatment response in several studies in diagnostic childhood ALL samples. 42,67,68 In conclusion, this study is the first to describe an association between the differential expression of key apoptosis genes and lineage, genetic subtype, and in vitro drug resistance in children with ALL. In addition, we identified a single gene, BCL2L13, which is related to both L-asparaginase resistance and treatment outcome independent from known prognostic factors in 2 independent cohorts of children with B-lineage ALL.…”

Gene expression shift towards normal B cells, decreased proliferative capacity and distinct surface receptors characterize leukemic blasts persisting during induction therapy in childhood acute lymphoblastic leukemia

“…4,5 Microarray-based gene expression profiling has been used to identify prognosis-associated signatures in childhood acute lymphoblastic leukemia (ALL). [6][7][8][9][10] It has also led to a large set of genes, which are potentially involved in GC response. [11][12][13][14][15] Accordingly, the hypotheses generated to explain the cytotoxic activity of GC are explicitly diverse, reaching from the direct activation of the apoptotic machinery to indirect deregulations of cellular functions, such as nucleotide and protein synthesis, energy metabolism, pH state and redox homeostasis.…”