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Thoas Fioretos

Thoas Fioretos

Research team manager

Thoas Fioretos

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

Summary, in 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.

Department/s

  • Division of Clinical Genetics
  • Computational Biology and Biological Physics - Undergoing reorganization
  • Paediatrics (Lund)
  • Division of Hematology and Transfusion Medicine
  • Mathematics (Faculty of Engineering)
  • The pathogenetic mechanisms behind MLL-rearranged acute leukemia in infancy

Publishing year

2007

Language

English

Pages

1198-1203

Publication/Series

Leukemia

Volume

21

Issue

6

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Cancer and Oncology

Keywords

  • gene expression profiling
  • pediatric leukemia
  • supervised
  • classification
  • ALL
  • AML

Status

Published

Research group

  • The pathogenetic mechanisms behind MLL-rearranged acute leukemia in infancy

ISBN/ISSN/Other

  • ISSN: 1476-5551