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Acute Leukemias

Combined high-resolution array-based comparative genomic hybridization and expression profiling of ETV6/RUNX1-positive acute lymphoblastic leukemias reveal a high incidence of cryptic Xq duplications and identify several putative target genes within the commonly gained region

Leukemia volume 21, pages 2137–2144 (2007)Cite this article

Abstract

Seventeen ETV6/RUNX1-positive pediatric acute lymphoblastic leukemias were investigated by high-resolution array-based comparative genomic hybridization (array CGH), gene expression profiling and fluorescence in situ hybridization. Comparing the array CGH and gene expression patterns revealed that genomic imbalances conferred a great impact on the expression of genes in the affected regions. The array CGH analyses identified a high frequency of cytogenetically cryptic genetic changes, for example, del(9p) and del(12p). Interestingly, a duplication of Xq material, varying between 30 and 60 Mb in size, was found in 6 of 11 males (55%), but not in females. Genes on Xq were found to have a high expression level in cases with dup(Xq); a similar overexpression was confirmed in t(12;21)-positive cases in an external gene expression data set. By studying the expression profile and the proposed function of genes in the minimally gained region, several candidate target genes (SPANXB, HMGB3, FAM50A, HTATSF1 and RAP2C) were identified. Among them, the testis-specific SPANXB gene was the only one showing a high and uniform overexpression, irrespective of gender and presence of Xq duplication, suggesting that this gene plays an important pathogenetic role in t(12;21)-positive leukemia.

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Acknowledgements

This work has been supported by grants from the Swedish Children's Cancer Foundation, the Swedish Cancer Society, the Swedish Research Council and the Medical Faculty at Lund University. We thank the Swegene DNA Microarray Resource Center in Lund, supported by the Knut and Alice Wallenberg Foundation through the Swegene consortium, for providing BAC arrays.

The expression data discussed in this publication have been deposited in NCBI's Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/) and are accessible through GEO Series accession number GSE7186.

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Authors and Affiliations

  1. Department of Clinical Genetics, Lund University Hospital, Lund, Sweden

    H Lilljebjörn, M Heidenblad, B Nilsson, C Lassen, A Horvat, B Johansson, A Andersson & T Fioretos

  2. Department of Pediatrics, Lund University Hospital, Lund, Sweden

    J Heldrup

  3. Department of Pediatrics, Linköping University Hospital, Linköping, Sweden

    M Behrendtz

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  1. H Lilljebjörn
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  2. M Heidenblad
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Correspondence to H Lilljebjörn.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Lilljebjörn, H., Heidenblad, M., Nilsson, B. et al. Combined high-resolution array-based comparative genomic hybridization and expression profiling of ETV6/RUNX1-positive acute lymphoblastic leukemias reveal a high incidence of cryptic Xq duplications and identify several putative target genes within the commonly gained region. Leukemia 21, 2137–2144 (2007). https://doi.org/10.1038/sj.leu.2404879

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