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Down Syndrome

Distinct gene signatures of transient and acute megakaryoblastic leukemia in Down syndrome

Leukemia volume 18, pages 1617–1623 (2004)Cite this article

Abstract

Approximately 10% of newborns with Down syndrome develop Transient Leukemia (TL), a disorder that is unique to infants with constitutional trisomy 21 (or trisomy 21 mosaicism). TL blasts disappear spontaneously within the first 3 months of life in the majority of cases. Despite the resolution of TL, 20–30% of these newborns will go on to develop acute megakaryoblastic leukemia (AMKL) later in life. In this study, samples from both TL and AMKL patients were examined using cDNA microarrays to study the pathogenic progression from TL to AMKL. TL and AMKL samples partition separately by cluster analysis, and AMKL samples had substantial increases in apolipoprotein C-I, transporter 1, myosin alkali light chain 4, and spermidine/spermine N-acetyltransferase, compared to TL samples. Although these findings will require validation in an independent series of TL and AMKL samples, they indicate that TL and AMKL have distinct gene signatures, and provide a basis for studies of the different mechanisms underlying either the resolution of TL or its progression to AMKL.

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Acknowledgements

We thank Mona Prasad for technical assistance and Dr Jeremy Squire for helpful comments. This work was supported by a Genome Canada grant to Dr Jim Woodgett (Scientific Director, UHN Microarray Centre).

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Author notes

  1. J Lightfoot

    Present address: Lorus Therapeutics Inc., Toronto, ON M9W 4Z7, Canada

  2. P F Macgregor

    Present address: Canadian Breast Cancer Research Alliance, Toronto, ON M5G 1N8, Canada

Authors and Affiliations

  1. Microarray Centre, Clinical Genomics Centre, University Health Network, Toronto, Ontario, Canada

    J Lightfoot, M Albert & P F Macgregor

  2. Division of Hematology/Oncology and Program for Developmental Biology, The Hospital for Sick Children, Toronto, Ontario, Canada

    J K Hitzler & A Zipursky

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  1. J Lightfoot
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  2. J K Hitzler
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  4. M Albert
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  5. P F Macgregor
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Corresponding author

Correspondence to P F Macgregor.

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Lightfoot, J., Hitzler, J., Zipursky, A. et al. Distinct gene signatures of transient and acute megakaryoblastic leukemia in Down syndrome. Leukemia 18, 1617–1623 (2004). https://doi.org/10.1038/sj.leu.2403466

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