Myeloid leukemia with promyelocytic features in transgenic mice expressing hCG-NuMA-RARα Journal Article
| Authors: | Sukhai, M. A.; Wu, X.; Xuan, Y.; Zhang, T.; Reis, P. P.; Dubé, K.; Rego, E. M.; Bhaumik, M.; Bailey, D. J.; Wells, R. A.; Kamel-Reid, S.; Pandolfi, P. P. |
| Article Title: | Myeloid leukemia with promyelocytic features in transgenic mice expressing hCG-NuMA-RARα |
| 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 (RARα). To date, five RARα partner genes have been identified in APL. NuMA-RARα was identified in a pediatric case of APL carrying a translocation t(11;17)(q13;q21). Using a construct containing the NuMA-RARα fusion gene driven by the human cathepsin G promoter (hCG-NuMA-RARα), 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-RARα is therefore sufficient for disease development in this APL model. |
| Keywords: | controlled study; unclassified drug; promoter region; myeloproliferative disorder; clinical feature; nonhuman; animal cell; mouse; animals; mice; animal tissue; gene expression; bone marrow; animal experiment; animal model; protein; genotype; cell differentiation; morphology; transgenic mouse; animalia; mus musculus; mice, transgenic; nuclear proteins; neutrophil; serine endopeptidases; gene identification; leukemia, myeloid; fusion gene; hematopoietic stem cells; chromosome translocation; base sequence; immunophenotyping; cathepsins; dna primers; acute promyelocytic leukemia; retinoic acid receptor alpha; myeloid leukemia; antigens, nuclear; receptors, retinoic acid; immunophenotype; granulopoiesis; cathepsin g; nuclear matrix-associated proteins; humans; priority journal; article; numa-rarα; transgenic model; nuclear mitotic apparatus protein |
| Journal Title: | Oncogene |
| Volume: | 23 |
| Issue: | 3 |
| ISSN: | 0950-9232 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2004-01-22 |
| Start Page: | 665 |
| End Page: | 678 |
| Language: | English |
| DOI: | 10.1038/sj.onc.1207073 |
| PROVIDER: | scopus |
| PUBMED: | 14737102 |
| DOI/URL: | |
| Notes: | Oncogene -- Cited By (since 1996):27 -- Export Date: 16 June 2014 -- CODEN: ONCNE -- Source: Scopus |
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