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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.

Author:
  • Anna Andersson
  • Cecilia Ritz
  • David Lindgren
  • Patrik Edén
  • Carin Lassen
  • Jesper Heldrup
  • Tor Olofsson
  • Johan Råde
  • Magnus Fontes
  • A Porwit-Macdonald
  • M Behrendtz
  • Mattias Höglund
  • Bertil Johansson
  • Thoas Fioretos
Publishing year: 2007
Language: English
Pages: 1198-1203
Publication/Series: Leukemia
Volume: 21
Issue: 6
Document type: Journal article
Publisher: Nature Publishing Group

Abstract english

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.

Keywords

  • Cancer and Oncology
  • gene expression profiling
  • pediatric leukemia
  • supervised
  • classification
  • ALL
  • AML

Other

Published
  • The pathogenetic mechanisms behind MLL-rearranged acute leukemia in infancy
  • ISSN: 1476-5551
Thoas Fioretos
E-mail: thoas.fioretos [at] med.lu.se

Principal investigator

Division of Clinical Genetics

+46 46 222 45 95

+46 70 334 33 67

BMC C13

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