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.

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.

• 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
• Department/s: Division of Clinical Genetics; Computational Biology and Biological Physics - Has been reorganised; 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
• Links: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17410184&dopt=Abstract; http://dx.doi.org/10.1038/sj.leu.2404688
• 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