1. ¹Microarray Centre, Clinical Genomics Centre, University Health Network, Toronto, Ontario, Canada
2. ²Division of Hematology/Oncology and Program for Developmental Biology, The Hospital for Sick Children, Toronto, Ontario, Canada

Correspondence: Dr PF Macgregor, CBCRA, 790 Bay Street, Suite 1000, Toronto, ON M5G 1N8, Canada. Fax: +1 416 596 1714; E-mail: pfmacgregor@cbcf.org

³Current address: Lorus Therapeutics Inc., Toronto, ON M9W 4Z7, Canada

⁴Current address: Canadian Breast Cancer Research Alliance, Toronto, ON M5G 1N8, Canada

Received 21 April 2004; Accepted 2 July 2004; Published online 2 September 2004.

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.