Prospective gene expression analysis accurately subtypes acute leukaemia in children and establishes a commonality between hyperdiploidy and t(12;21) in acute lymphoblastic leukaemia

Frederik W. Van Delft, Tony Bellotti, Zhiyuan Luo, Louise K. Jones, Naina Patel, Olga Yiannikouris, Alex S. Hill, Mike Hubank, Helena Kempski, Danielle Fletcher, Tracy Chaplin, Nicola Foot, Bryan D. Young, Ian M. Hann, Alex Gammerman, Vaskar Saha

Research output: Journal PublicationArticlepeer-review

35 Citations (Scopus)

Abstract

We have prospectively analysed and correlated the gene expression profiles of children presenting with acute leukaemia to the Royal London and Great Ormond Street Hospitals with morphological diagnosis, immunophenotype and karyotype. Total RNA extracted from freshly sorted blast cells was obtained from 84 lymphoblastic [acute lymphoblastic leukaemia (ALL)], 20 myeloid [acute myeloid leukaemia (AML)] and three unclassified acute leukaemias and hybridised to the high density Affymetrix U133A oligonucleotide array. Analysis of variance and significance analysis of microarrays was used to identify discriminatory genes. A novel 50-gene set accurately identified all patients with ALL and AML and predicted for a diagnosis of AML in three patients with unclassified acute leukaemia. A unique gene set was derived for each of eight subtypes of acute leukaemia within our data set. A common profile for children with ALL with an ETV6-RUNX1 fusion, amplification or deletion of ETV6, amplification of RUNX1 or hyperdiploidy with an additional chromosome 21 was identified. This suggests that these rearrangements share a commonality in biological pathways that maintains the leukaemic state. The gene TERF2 was most highly expressed in this group of patients. Our analyses demonstrate that not only is microarray analysis the single most effective tool for the diagnosis of acute leukaemias of childhood but it has the ability to identify unique biological pathways. To further evaluate its prognostic value it needs to be incorporated into the routine diagnostic analysis for large-scale clinical trials in childhood acute leukaemias.

Original languageEnglish
Pages (from-to)26-35
Number of pages10
JournalBritish Journal of Haematology
Volume130
Issue number1
DOIs
Publication statusPublished - 2005
Externally publishedYes

Keywords

  • Childhood haematological malignancies
  • Gene expression
  • Mathematical modelling
  • Molecular diagnostics
  • Telomere

ASJC Scopus subject areas

  • Hematology

Fingerprint

Dive into the research topics of 'Prospective gene expression analysis accurately subtypes acute leukaemia in children and establishes a commonality between hyperdiploidy and t(12;21) in acute lymphoblastic leukaemia'. Together they form a unique fingerprint.

Cite this