Modeling acute promyelocytic leukemia in the mouse: New insights in the pathogenesis of human leukemias Journal Article
| Authors: | Merghoub, T.; Gurrieri, C.; Piazza, F.; Pandolfi, P. P. |
| Article Title: | Modeling acute promyelocytic leukemia in the mouse: New insights in the pathogenesis of human leukemias |
| Abstract: | Acute promyelocytic leukemia (APL) is characterized by the expansion of malignant myeloid cells blocked at the promyelocytic stage of differentiation and is associated with reciprocal chromosomal translocations always involving the retinoic acid receptor alpha (RAR alpha) gene on chromosome 17. As a consequence of the translocation, RAR alpha variably fuses to the PML, PLZF, NPM, NuMA, and Stat5b genes (X genes), respectively, leading to the generation of RAR alpha -X and X-RAR alpha fusion genes. The aberrant chimeric proteins encoded by these genes, as well as the inactivation of the X and RAR alpha functions, may exert a crucial role in leukemogenesis. To define the molecular genetics of APL and the contribution of each molecular event in APL pathogenesis, we have generated transgenic mice harboring X-RAR alpha and/or RAR alpha -X genes as well as mice where the various X genes have been inactivated by homologous recombination. Here we show that while the X-RARa fusion gene is crucial for leukemogenesis, the presence of RARa-X and the inactivation of X function are critical in modulating the onset as well as the phenotype of the leukemia, (C) 2001 Academic Press. |
| Keywords: | leukemia; gene; cytogenetics; fusion; cell-growth; dna-binding; chromosomal translocation; pml-rar-alpha; trans-retinoic acid; zinc-finger protein; hematopoietic progenitors; acid receptor-alpha; nuclear matrix protein; cancer; molecular pathogenesis |
| Journal Title: | Blood Cells, Molecules, and Diseases |
| Volume: | 27 |
| Issue: | 1 |
| ISSN: | 1079-9796 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2001-01-01 |
| Start Page: | 231 |
| End Page: | 248 |
| Language: | English |
| ACCESSION: | WOS:000167738300028 |
| DOI: | 10.1006/bcmd.2001.0385 |
| PROVIDER: | wos |
| PUBMED: | 11358384 |
| Notes: | Article -- Source: Wos |
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