Myeloid leukemia with promyelocytic features in transgenic mice expressing hCG-NuMA-RARα
- 22 January 2004
- journal article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 23 (3), 665-678
- https://doi.org/10.1038/sj.onc.1207073
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.Keywords
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