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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Jun 1;89(11):4840–4844. doi: 10.1073/pnas.89.11.4840

Expression pattern of the RAR alpha-PML fusion gene in acute promyelocytic leukemia.

M Alcalay 1, D Zangrilli 1, M Fagioli 1, P P Pandolfi 1, A Mencarelli 1, F Lo Coco 1, A Biondi 1, F Grignani 1, P G Pelicci 1
PMCID: PMC49183  PMID: 1317574

Abstract

Two chimeric genes, PML-RAR alpha and RAR alpha-PML, are formed as a consequence of the acute promyelocytic leukemia (APL)-specific reciprocal translocation of chromosomes 15 and 17 [t(15;17)]. PML-RAR alpha is expressed as a fusion protein. We investigated the organization and expression pattern of the RAR alpha-PML gene in a series of APL patients representative of the molecular heterogeneity of the t(15;17) and found (i) two types of RAR alpha-PML mRNA junctions (RAR alpha exon 2/PML exon 4 or RAR alpha exon 2/PML exon 7) that maintain the RAR alpha and PML longest open reading frames aligned and are the result of chromosome 15 breaking at two different sites; and (ii) 10 different RAR alpha-PML fusion transcripts that differ for the assembly of their PML coding exons. A RAR alpha-PML transcript was present in most, but not all, APL patients.

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Selected References

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  1. Alcalay M., Zangrilli D., Pandolfi P. P., Longo L., Mencarelli A., Giacomucci A., Rocchi M., Biondi A., Rambaldi A., Lo Coco F. 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):1977–1981. doi: 10.1073/pnas.88.5.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Biondi A., Rambaldi A., Alcalay M., Pandolfi P. P., Lo Coco F., Diverio D., Rossi V., Mencarelli A., Longo L., Zangrilli D. RAR-alpha gene rearrangements as a genetic marker for diagnosis and monitoring in acute promyelocytic leukemia. Blood. 1991 Apr 1;77(7):1418–1422. [PubMed] [Google Scholar]
  3. Borrow J., Goddard A. D., Sheer D., Solomon E. Molecular analysis of acute promyelocytic leukemia breakpoint cluster region on chromosome 17. Science. 1990 Sep 28;249(4976):1577–1580. doi: 10.1126/science.2218500. [DOI] [PubMed] [Google Scholar]
  4. Collins S. J., Robertson K. A., Mueller L. Retinoic acid-induced granulocytic differentiation of HL-60 myeloid leukemia cells is mediated directly through the retinoic acid receptor (RAR-alpha). Mol Cell Biol. 1990 May;10(5):2154–2163. doi: 10.1128/mcb.10.5.2154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Evans R. M. The steroid and thyroid hormone receptor superfamily. Science. 1988 May 13;240(4854):889–895. doi: 10.1126/science.3283939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Giguere V., Ong E. S., Segui P., Evans R. M. Identification of a receptor for the morphogen retinoic acid. Nature. 1987 Dec 17;330(6149):624–629. doi: 10.1038/330624a0. [DOI] [PubMed] [Google Scholar]
  7. Green S., Chambon P. Nuclear receptors enhance our understanding of transcription regulation. Trends Genet. 1988 Nov;4(11):309–314. doi: 10.1016/0168-9525(88)90108-4. [DOI] [PubMed] [Google Scholar]
  8. Kakizuka A., Miller W. H., Jr, Umesono K., Warrell R. P., Jr, Frankel S. R., Murty V. V., Dmitrovsky E., Evans R. M. Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML. Cell. 1991 Aug 23;66(4):663–674. doi: 10.1016/0092-8674(91)90112-c. [DOI] [PubMed] [Google Scholar]
  9. Lo Coco F., Avvisati G., Diverio D., Petti M. C., Alcalay M., Pandolfi P. P., Zangrilli D., Biondi A., Rambaldi A., Moleti M. L. Molecular evaluation of response to all-trans-retinoic acid therapy in patients with acute promyelocytic leukemia. Blood. 1991 Apr 15;77(8):1657–1659. [PubMed] [Google Scholar]
  10. Longo L., Pandolfi P. P., Biondi A., Rambaldi A., Mencarelli A., Lo Coco F., Diverio D., Pegoraro L., Avanzi G., Tabilio A. Rearrangements and aberrant expression of the retinoic acid receptor alpha gene in acute promyelocytic leukemias. J Exp Med. 1990 Dec 1;172(6):1571–1575. doi: 10.1084/jem.172.6.1571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Pandolfi P. P., Alcalay M., Fagioli M., Zangrilli D., Mencarelli A., Diverio D., Biondi A., Lo Coco F., Rambaldi A., Grignani F. Genomic variability and alternative splicing generate multiple PML/RAR alpha transcripts that encode aberrant PML proteins and PML/RAR alpha isoforms in acute promyelocytic leukaemia. EMBO J. 1992 Apr;11(4):1397–1407. doi: 10.1002/j.1460-2075.1992.tb05185.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Pandolfi P. P., Grignani F., Alcalay M., Mencarelli A., Biondi A., LoCoco F., Grignani F., Pelicci P. G. 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):1285–1292. [PubMed] [Google Scholar]
  13. Petkovich M., Brand N. J., Krust A., Chambon P. A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature. 1987 Dec 3;330(6147):444–450. doi: 10.1038/330444a0. [DOI] [PubMed] [Google Scholar]
  14. de Thé H., Chomienne C., Lanotte M., Degos L., Dejean A. The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus. Nature. 1990 Oct 11;347(6293):558–561. doi: 10.1038/347558a0. [DOI] [PubMed] [Google Scholar]
  15. de Thé H., Lavau C., Marchio A., Chomienne C., Degos L., Dejean A. The PML-RAR alpha fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR. Cell. 1991 Aug 23;66(4):675–684. doi: 10.1016/0092-8674(91)90113-d. [DOI] [PubMed] [Google Scholar]

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