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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.

Andersson, Anna LU orcid ; Ritz, Cecilia LU ; Lindgren, David LU ; Edén, Patrik LU ; Lassen, Carin LU ; Heldrup, Jesper LU ; Olofsson, Tor LU ; Råde, Johan LU ; Fontes, Magnus LU and Porwit-Macdonald, A , et al. (2007) In Leukemia 21(6). p.1198-1203
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
@article{2b83d73e-e3ea-494d-a63c-4c87873cfc64,
  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.}},
  author       = {{Andersson, Anna and Ritz, Cecilia and Lindgren, David and Edén, Patrik and Lassen, Carin and Heldrup, Jesper and Olofsson, Tor and Råde, Johan and Fontes, Magnus and Porwit-Macdonald, A and Behrendtz, M and Höglund, Mattias and Johansson, Bertil and Fioretos, Thoas}},
  issn         = {{1476-5551}},
  keywords     = {{gene expression profiling; pediatric leukemia; supervised; classification; ALL; AML}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{1198--1203}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Leukemia}},
  title        = {{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.}},
  url          = {{http://dx.doi.org/10.1038/sj.leu.2404688}},
  doi          = {{10.1038/sj.leu.2404688}},
  volume       = {{21}},
  year         = {{2007}},
}