| Literature DB >> 14737102 |
Mahadeo A Sukhai1, Xuemei Wu, Yali Xuan, Tong Zhang, Patricia P Reis, Karina Dubé, Eduardo M Rego, Mantu Bhaumik, Denis J Bailey, Richard A Wells, Suzanne Kamel-Reid, Pier Paolo Pandolfi.
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 (RARalpha). To date, five RARalpha partner genes have been identified in APL. NuMA-RARalpha was identified in a pediatric case of APL carrying a translocation t(11;17)(q13;q21). Using a construct containing the NuMA-RARalpha fusion gene driven by the human cathepsin G promoter (hCG-NuMA-RARalpha), 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-RARalpha is therefore sufficient for disease development in this APL model.Entities:
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Year: 2004 PMID： 14737102 DOI： 10.1038/sj.onc.1207073
Source DB: PubMed Journal: Oncogene ISSN： 0950-9232 Impact factor: 9.867