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- Title
Myeloid leukemia with promyelocytic features in transgenic mice expressing hCG-NuMA-RARa.
- Authors
Sukhai, Mahadeo A.; Xuemei Wu; Yali Xuan, Mahadeo A.; Tong Zhang; Reis, Patricia P.; Dubé, Karina; Rego, Eduardo M.; Bhaumik, Mantu; Bailey, Denis J.; Wells, Richard A.; Kamel-Reid, Suzanne; Pandolfi, Pier Paolo
- 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 (RARa). To date, five RARa partner genes have been identified in APL. NuMA-RARa was identified in a pediatric case of APL carrying a translocation t(11;17)(q13;q21). Using a construct containing the NuMA-RARa fusion gene driven by the human cathepsin G promoter (hCG-NuMA-RARa), 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-RARa is therefore sufficient for disease development in this APL model.Oncogene (2004) 23, 665-678. doi:10.1038/sj.onc.1207073
- Subjects
LEUKEMIA; ACUTE leukemia; CHROMOSOMES; TRANSGENIC mice; NEUTROPHILS
- Publication
Oncogene, 2004, Vol 23, Issue 3, p665
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1207073