The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus
- PMID: 2170850
- DOI: 10.1038/347558a0
The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus
Abstract
Retinoic acid is a vitamin A derivative with striking effects on development and cell differentiation. Several nuclear retinoic acid receptors (RARs), acting as ligand-inducible transcription factors, have been characterized and indirect evidence suggests that they have distinct roles. One of the most intriguing properties of retinoic acid is its ability to induce in vivo differentiation of acute promyelocytic leukaemia (APL) cells into mature granulocytes, leading to morphological complete remissions. Because the RAR alpha gene maps to chromosome 17q21 (ref. 14), close to the t(15;17) (q21-q11-22) translocation specifically associated with APL, we analysed RAR alpha gene structure and expression in APL cells. We report here that, in one APL-derived cell line, the RAR alpha gene has been translocated to a locus, myl, on chromosome 15, resulting in the synthesis of a myl/RAR alpha fusion messenger RNA. Using two probes located on either side of the cloned breakpoint, we have found genomic rearrangements of one or other locus in six patients out of eight, demonstrating that the RAR alpha and/or myl genes are frequently rearranged in APL and the breakpoints are clustered. These findings strongly implicate retinoic acid receptor alpha in leukaemogenesis.
Similar articles
-
Structure and origin of the acute promyelocytic leukemia myl/RAR alpha cDNA and characterization of its retinoid-binding and transactivation properties.Oncogene. 1991 Jul;6(7):1285-92. Oncogene. 1991. PMID: 1650447
-
Occurrence of distinct PML-RAR-alpha fusion gene isoforms in patients with acute promyelocytic leukemia detected by reverse transcriptase/polymerase chain reaction.Oncogene. 1992 Jun;7(6):1223-32. Oncogene. 1992. PMID: 1375719
-
Rearrangements of the retinoic acid receptor alpha and promyelocytic leukemia zinc finger genes resulting from t(11;17)(q23;q21) in a patient with acute promyelocytic leukemia.J Clin Invest. 1993 May;91(5):2260-7. doi: 10.1172/JCI116453. J Clin Invest. 1993. PMID: 8387545 Free PMC article.
-
[Mechanism of action of retinoids in a new therapeutic approach to acute promyelocytic leukemia].Bull Cancer. 1992;79(7):697-704. Bull Cancer. 1992. PMID: 1334741 Review. French.
-
Gene rearrangements in the molecular pathogenesis of acute promyelocytic leukemia.J Cell Physiol. 1997 Nov;173(2):288-96. doi: 10.1002/(SICI)1097-4652(199711)173:2<288::AID-JCP38>3.0.CO;2-9. J Cell Physiol. 1997. PMID: 9365539 Review.
Cited by
-
Interleukin 6 signaling regulates promyelocytic leukemia protein gene expression in human normal and cancer cells.J Biol Chem. 2012 Aug 3;287(32):26702-14. doi: 10.1074/jbc.M111.316869. Epub 2012 Jun 18. J Biol Chem. 2012. PMID: 22711534 Free PMC article.
-
Phase transition of a disordered nuage protein generates environmentally responsive membraneless organelles.Mol Cell. 2015 Mar 5;57(5):936-947. doi: 10.1016/j.molcel.2015.01.013. Mol Cell. 2015. PMID: 25747659 Free PMC article.
-
Differences in the action and metabolism between retinol and retinoic acid in B lymphocytes.J Cell Biol. 1991 Nov;115(3):851-9. doi: 10.1083/jcb.115.3.851. J Cell Biol. 1991. PMID: 1655814 Free PMC article.
-
Translocation breakpoint of acute promyelocytic leukemia lies within the retinoic acid receptor alpha locus.Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1977-81. doi: 10.1073/pnas.88.5.1977. Proc Natl Acad Sci U S A. 1991. PMID: 1848017 Free PMC article.
-
In vivo temporal resolution of acute promyelocytic leukemia progression reveals a role of Klf4 in suppressing early leukemic transformation.Genes Dev. 2022 Apr 1;36(7-8):451-467. doi: 10.1101/gad.349115.121. Epub 2022 Apr 21. Genes Dev. 2022. PMID: 35450883 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases