1. ¹Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
2. ²Department of Cellular and Molecular Biology, the Ontario Cancer Institute/University Health Network, Toronto, Ontario, Canada
3. ³Molecular and Developmental Biology Lab, Molecular Biology Program and Department of Pathology, Memorial Sloan Kettering Cancer Center, Sloan Kettering Institute, New York, NY, USA
4. ⁴Department of Pathology, The Ontario Cancer Institute/University Health Network, Toronto, Ontario, Canada
5. ⁵Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

Correspondence: S Kamel-Reid, Princess Margaret Hospital/The Ontario Cancer Institute, Room 9-622, 610 University Avenue, Toronto, ON, Canada M5G 2M9. E-mail: s.kamel.reid@utoronto.ca

Received 13 June 2003; Revised 25 July 2003; Accepted 4 August 2003.

Abstract

Acute promyelocytic leukemia (APL) is characterized by the accumulation of abnormal promyelocytes in the bone marrow (BM), and by the presence of a reciprocal chromosomal translocation involving retinoic acid receptor alpha (RAR). To date, five RAR partner genes have been identified in APL. NuMA-RAR was identified in a pediatric case of APL carrying a translocation t(11;17)(q13;q21). Using a construct containing the NuMA-RAR fusion gene driven by the human cathepsin G promoter (hCG-NuMA-RAR), two transgenic mouse lines were generated. Transgenic mice were observed to have a genetic myeloproliferation (increased granulopoiesis in BM) at an early age, and rapidly developed a myeloproliferative disease-like myeloid leukemia. This leukemia was morphologically and immunophenotypically indistinguishable from human APL, with a penetrance of 100%. The phenotype of transgenic mice was consistent with a blockade of neutrophil differentiation. NuMA-RAR is therefore sufficient for disease development in this APL model.