| Abstract: |
Acute promyelocytic leukemia (APL) is characterized by reciprocal chromosomal translocations that always involve the retinoic acid receptor-α (RARα) gene on chromosome 17. RARα variably fuses to the PML, PLZF, NPM, NuMA, and STAT 5b genes (X genes), leading to the generation of X-RARα and RARα-X fusion genes. The aberrant X-RARα proteins retain the dimerization domains of their parental proteins and therefore can act as dominant negative oncogenic products on both RARα/RXR and X pathways. Studies in transgenic mice harboring X-RARα and RARα-X fusion genes and in mice lacking X genes have helped unravel the molecular mechanisms underlying APL leukemogenesis, which lead to the development of novel therapeutic strategies. Moreover, transgenic mouse models of APL were useful to test in vivo the efficacy of these novel therapeutic approaches as well as of drug combinations such as retinoic acid and As203 that were previously known to be effective as single agents in human APL. Semin Hematol 38:54-70. Copyright © 2001 by W.B. Saunders Company. |
| Keywords: |
controlled study; unclassified drug; drug efficacy; nonhuman; treatment planning; antineoplastic agents; molecular genetics; animal cell; mouse; animals; mice; disease association; cell protein; animal experiment; animal model; mice, transgenic; arsenic trioxide; leukemia, promyelocytic, acute; hybrid protein; leukemogenesis; acute myeloblastic leukemia; fusion gene; oncogene proteins, fusion; chromosome translocation; dimerization; disease models, animal; zinc finger protein; retinoic acid; chromosome 17; retinoic acid receptor alpha; retinoic acid receptor; nucleophosmin; stat5b protein; humans; priority journal; article; protein nuclear mitotic apparatus; protein promyelocyte leukemia zinc finger
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