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Gene expression analysis reveals HOX gene upregulation in trisomy 8 AML

Leukemia volume 24, pages 1239–1243 (2010)Cite this article

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Acute myeloid leukemia (AML) is a heterogeneous disease. Among chromosomal numerical aberrations, trisomy 8 (+8) is the most common chromosomal change, conferring an intermediate prognosis, and is associated with the t(7;12), t(9;11) and t(1;11) translocations.1 Alone, trisomy 8 does not appear to be sufficient for leukemogenesis but may be associated with an increased risk of myeloid malignancy.1 To investigate further the contribution of +8 to AML, we determined the gene expression signature associated specifically with this numerical chromosomal abnormality using large, previously reported, AML microarray data sets2, 3 and data sets derived from AML cell lines. We have identified a novel association between HOXA gene upregulation and +8 AML providing new insight into the potential contribution of +8 to AML pathogenesis.

The mechanism underlying the upregulation of the HOXA genes in the +8 AML group is unknown. In AML with the t(9;11) translocations, altered HOX gene expression is associated with the aberrant function of the MLL fusion protein.6 We have excluded samples with the t(9;11) (MLL translocation) in this analysis of +8 AML patients; however, we cannot exclude the presence of the MLL partial tandem duplications that can also upregulate HOXA9 expression.7 In normal karyotype AML, the mechanism associated with increased expression of HOX genes appears to be distinct from AML with MLL fusions and may be associated with NPM1 mutations.8

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Acknowledgements

CHK was supported by a scholarship from the Queen Elizabeth Hospital Research Foundation and ALB was a fellow of the Cancer Council of South Australia.

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Authors and Affiliations

  1. The Basil Hetzel Institute, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia

    C H Kok & R J D'Andrea

  2. Centre for Stem Cell Research, The University of Adelaide, Adelaide, South Australia, Australia

    C H Kok, A L Brown & R J D'Andrea

  3. Centre for Cancer Biology, SA Pathology, Adelaide, South Australia, Australia

    C H Kok, A L Brown & R J D'Andrea

  4. Children's Cancer Centre, Murdoch Children's Research Institute, Melbourne, Victoria, Australia

    P G Ekert

  5. Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Parkville, Victoria, Australia

    P G Ekert

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  1. C H Kok
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  2. A L Brown
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Correspondence to R J D'Andrea.

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Kok, C., Brown, A., Ekert, P. et al. Gene expression analysis reveals HOX gene upregulation in trisomy 8 AML. Leukemia 24, 1239–1243 (2010). https://doi.org/10.1038/leu.2010.85

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