TitleTranslocations of the RARalpha gene in acute promyelocytic leukemia.
Publication TypeJournal Article
Year of Publication2001
AuthorsZelent, A, Guidez F, Melnick A, Waxman S, and Licht J D.
JournalOncogene
Volume20
Issue49
Pagination7186-203
Date Published2001 Oct 29
ISSN0950-9232
KeywordsAntigens, Nuclear, Cell Cycle Proteins, DNA-Binding Proteins, Humans, Leukemia, Promyelocytic, Acute, Milk Proteins, Neoplasm Proteins, Nuclear Matrix-Associated Proteins, Nuclear Proteins, Nucleophosmin, Oncogene Proteins, Fusion, Receptors, Retinoic Acid, Retinoic Acid Receptor alpha, STAT5 Transcription Factor, Trans-Activators, Translocation, Genetic, Tretinoin
Abstract

<p>Acute promyelocytic leukemia (APL) has been recognized as a distinct clinical entity for over 40 years. Although relatively rare among hematopoietic malignancies (approximately 10% of AML cases), this disease has attracted a particularly good share of attention by becoming the first human cancer in which all-trans-retinoic acid (ATRA), a physiologically active derivative of vitamin A, was able to induce complete remission (CR). ATRA induced remission is not associated with rapid cell death, as in the case of conventional chemotherapy, but with a restoration of the 'normal' granulocytic differentiation pathway. With this remarkable medical success story APL has overnight become a paradigm for the differentiation therapy of cancer. A few years later, excitement with APL was further enhanced by the discovery that a cytogenetic marker for this disease, the t(15:17) reciprocal chromosomal translocation, involves a fusion between the retinoic acid receptor alpha (RARalpha) gene and a previously unknown locus named promyelocytic leukemia (PML). Consequence of this gene rearrangement is expression of the PML-RARalpha chimeric oncoprotein, which is responsible for the cellular transformation as well as ATRA response that is observed in APL. Since this initial discovery, a number of different translocation partner genes of RARalpha have been reported in rarer cases of APL, strongly suggesting that disruption of RARalpha underlies its pathogenesis. This article reviews various rearrangements of the RARalpha gene that have so far been described in literature, functions of the proteins encoded by the different RARalpha partner loci, and implications that these may have for the molecular pathogenesis of APL.</p>

DOI10.1038/sj.onc.1204766
Alternate JournalOncogene
PubMed ID11704847
Grant ListCA59936 / CA / NCI NIH HHS / United States
KO8 CA73762 / CA / NCI NIH HHS / United States