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- Kuchinskaya, E, et al.
(författare)
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Children and adults with acute lymphoblastic leukaemia have similar gene expression profiles
- 2005
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Ingår i: European Journal of Haematology. - Oxford : Blackwell Publishing. - 0902-4441 .- 1600-0609. ; 74:6, s. 466-480
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To compare the gene expression pattern in children and adults with acute lymphoblastic leukaemia (ALL) in order to improve our understanding of the difference in disease biology and prognosis.METHODS: The gene expression profiles in diagnostic samples from 29 children and 15 adults with ALL were analysed using the oligonucleotide chip Hu95ver2a, produced by Affymetrix.RESULTS: Unsupervised hierarchical cluster analysis revealed that, in spite of differences in outcome, patients clustered irrespective of age, first by T-cell or B-precursor immunophenotype, and second by cytogenetic changes within the B-precursor group. The expression pattern analysis allowed the reclassification of some samples into the proper cytogenetic group. We also showed that separate clustering of samples with the BCR/ABL translocation could be explained by different breakpoint regions in the BCR. No significant difference in gene expression was observed between samples with and without CDKN2A deletion within the B-precursor group. Analysis of different age groups revealed a similarity in expression profiles when infants with the MLL translocation and adults over 40 yr of age were compared irrespective of karyotype.CONCLUSIONS: In spite of the difference in clinical outcome, the gene expression pattern in children and adults with ALL is very similar and is primarily dependent on immunophenotype and cytogenetic aberrations. However, when age groups are compared, the expression patterns of infants and adults over 40 show a remarkable similarity.
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- Andersson, Anna, et al.
(författare)
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Microarray-based classification of a consecutive series of 121 childhood acute leukemias: prediction of leukemic and genetic subtype as well as of minimal residual disease status.
- 2007
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 21:6, s. 1198-1203
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Tidskriftsartikel (refereegranskat)abstract
- Gene expression analyses were performed on 121 consecutive childhood leukemias (87 B-lineage acute lymphoblastic leukemias (ALLs), 11 T-cell ALLs and 23 acute myeloid leukemias (AMLs)), investigated during an 8-year period at a single center. The supervised learning algorithm k-nearest neighbor was utilized to build gene expression predictors that could classify the ALLs/AMLs according to clinically important subtypes with high accuracy. Validation experiments in an independent data set verified the high prediction accuracies of our classifiers. B-lineage ALLs with uncharacteristic cytogenetic aberrations or with a normal karyotype displayed heterogeneous gene expression profiles, resulting in low prediction accuracies. Minimal residual disease status (MRD) in T-cell ALLs with a high (40.1%) MRD at day 29 could be classified with 100% accuracy already at the time of diagnosis. In pediatric leukemias with uncharacteristic cytogenetic aberrations or with a normal karyotype, unsupervised analysis identified two novel subgroups: one consisting mainly of cases remaining in complete remission (CR) and one containing a few patients in CR and all but one of the patients who relapsed. This study of a consecutive series of childhood leukemias confirms and extends further previous reports demonstrating that global gene expression profiling provides a valuable tool for genetic and clinical classification of childhood leukemias.
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