The Theory of APL Revisited
Acute promyelocytic leukemia (APL) is associated with reciprocal and balanced chromosomal translocations always involving the retinoic acid receptor α (RARα) gene on chromosome 17 and variable partner genes (X genes) on distinct chromosomes. RARα fuses to the PML gene in the majority of APL cases, and in a few cases to the PLZF, NPM, NuMA and STAT5b genes. As a consequence, X-RARα and RARα-X fusion genes are generated encoding aberrant chimeric proteins that exert critical oncogenic functions. Here we will integrate some of the most recent findings in APL research in a unified model and discuss some of the outstanding questions that remain to be addressed.
KeywordsFusion Protein Acute Promyelocytic Leukemia Retinoic Acid Receptor Transgenic Animal Model Retinoic Acid Receptor Alpha
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- Fogal V, Gostissa M, Sandy P, Zacvchi P, Sternsdorf K, Jensen K, Pandolfi PP, Will H, Schneider C, Del Sal G (2000) Regulation of p53 activity in nuclear bodies by a specific PML isoform. EMBO J 6:185–195Google Scholar
- Grignani F, De Matteis S, Nervi C, Tomassoni L, Gelmetti V, Cioce M, Fanelli M, Ruthardt M, Ferrara FF, Zamir I, Seiser C, Lazar MA, Minucci S, Pelicci PG (1998) Fusion proteins of the retinoic acid receptor-alpha recruit histone deacetylase in promyelocytic leukaemia. Nature 391:815–818PubMedCrossRefGoogle Scholar
- Minucci S, Monestiroli S, Giavara S, Ronzoni S, Marchesi F, Insinga A, Diverio D, Gasparini P, Capillo M, Colombo E, Matteucci C, Contegno F, Lo-Coco F, Scanziani E, Gobbi A, Pelicci PG (2002) PML-RAR induces promyelocytic leukemias with high efficiency following retroviral gene transfer into purified murine hematopoietic progenitors. Blood 100:2989–2995PubMedCrossRefGoogle Scholar
- Ruthardt M, Testa U, Nervi C, Ferrucci PF, Grignani F, Puccetti E, Grignani F, Peschle C, Pelicci PG (1997) Opposite effects of the acute promyelocytic leukemia PML-retinoic acid receptor alpha (RAR alpha) and PLZF-RAR alpha fusion proteins on retinoic acid signalling. Mol Cell Biol 17:4859–4869PubMedGoogle Scholar