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Logo of jcinvestThe Journal of Clinical Investigation
J Clin Invest. 1993 May; 91(5): 2260–2267.
PMCID: PMC288229

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.


Cytogenetic study of a patient with acute promyelocytic leukemia (APL) showed an unusual karyotype 46,xy,t(11;17) (q23;21) without apparent rearrangement of chromosome 15. Molecular studies showed rearrangements of the retinoic acid receptor alpha (RAR alpha) gene but no rearrangement of the promyelocytic leukemia gene consistent with the cytogenetic data. Similar to t(15;17) APL, all-trans retinoic acid treatment in this patient produced an early leukocytosis which was followed by a myeloid maturation, but the patient died too early to achieve remission. Further molecular analysis of this patient showed a rearrangement between the RAR alpha gene and a newly discovered zinc finger gene named PLZF (promyelocytic leukemia zinc finger). The fusion PLZF-RAR alpha gene found in this case, was not found in DNA obtained from the bone marrow of normals, APL with t(15;17) and in one patient with AML-M2 with a t(11;17). Fluorescence in situ hybridization using a PLZF specific probe localized the PLZF gene to chromosomal band 11q23.1. Partial exon/intron structure of the PLZF gene flanking the break point on chromosome 11 was also established and the breakpoint within the RAR alpha gene was mapped approximately 2 kb downstream of the exon encoding the 5' untranslated region and the unique A2 domain of the RAR alpha 2 isoform.

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Selected References

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  • Larson RA, Kondo K, Vardiman JW, Butler AE, Golomb HM, Rowley JD. Evidence for a 15;17 translocation in every patient with acute promyelocytic leukemia. Am J Med. 1984 May;76(5):827–841. [PubMed]
  • 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. [PubMed]
  • Borrow J, Goddard AD, Sheer D, Solomon E. Molecular analysis of acute promyelocytic leukemia breakpoint cluster region on chromosome 17. Science. 1990 Sep 28;249(4976):1577–1580. [PubMed]
  • Goddard AD, Borrow J, Freemont PS, Solomon E. Characterization of a zinc finger gene disrupted by the t(15;17) in acute promyelocytic leukemia. Science. 1991 Nov 29;254(5036):1371–1374. [PubMed]
  • 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. [PubMed]
  • Kakizuka A, Miller WH, Jr, Umesono K, Warrell RP, Jr, Frankel SR, Murty VV, Dmitrovsky E, Evans RM. 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. [PubMed]
  • Chen Z, Brand NJ, Chen A, Chen SJ, Tong JH, Wang ZY, Waxman S, Zelent A. Fusion between a novel Krüppel-like zinc finger gene and the retinoic acid receptor-alpha locus due to a variant t(11;17) translocation associated with acute promyelocytic leukaemia. EMBO J. 1993 Mar;12(3):1161–1167. [PubMed]
  • Lithotripsy. Health and Public Policy Committee, American College of Physicians. Ann Intern Med. 1985 Oct;103(4):626–629. [PubMed]
  • Bernard O, Guglielmi P, Jonveaux P, Cherif D, Gisselbrecht S, Mauchauffe M, Berger R, Larsen CJ, Mathieu-Mahul D. Two distinct mechanisms for the SCL gene activation in the t(1;14) translocation of T-cell leukemias. Genes Chromosomes Cancer. 1990 Jan;1(3):194–208. [PubMed]
  • Cherif D, Julier C, Delattre O, Derré J, Lathrop GM, Berger R. Simultaneous localization of cosmids and chromosome R-banding by fluorescence microscopy: application to regional mapping of human chromosome 11. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6639–6643. [PubMed]
  • Chen SJ, Chen Z, Chen A, Tong JH, Dong S, Wang ZY, Waxman S, Zelent A. 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):1223–1232. [PubMed]
  • Hagemeijer A, Bartram CR, Smit EM, van Agthoven AJ, Bootsma D. Is the chromosomal region 9q34 always involved in variants of the Ph1 translocation? Cancer Genet Cytogenet. 1984 Sep;13(1):1–16. [PubMed]
  • Najfeld V, Scalise A, Troy K. A new variant translocation 11;17 in a patient with acute promyelocytic leukemia together with t(7;12). Cancer Genet Cytogenet. 1989 Nov;43(1):103–108. [PubMed]
  • Hromas R, Collins SJ, Hickstein D, Raskind W, Deaven LL, O'Hara P, Hagen FS, Kaushansky K. A retinoic acid-responsive human zinc finger gene, MZF-1, preferentially expressed in myeloid cells. J Biol Chem. 1991 Aug 5;266(22):14183–14187. [PubMed]
  • Rowley JD, Diaz MO, Espinosa R, 3rd, Patel YD, van Melle E, Ziemin S, Taillon-Miller P, Lichter P, Evans GA, Kersey JH, et al. Mapping chromosome band 11q23 in human acute leukemia with biotinylated probes: identification of 11q23 translocation breakpoints with a yeast artificial chromosome. Proc Natl Acad Sci U S A. 1990 Dec;87(23):9358–9362. [PubMed]
  • Das S, Cotter FE, Gibbons B, Dhut S, Young BD. CD3G is within 200 kb of the leukemic t(4;11) translocation breakpoint. Genes Chromosomes Cancer. 1991 Jan;3(1):44–47. [PubMed]
  • Cimino G, Moir DT, Canaani O, Williams K, Crist WM, Katzav S, Cannizzaro L, Lange B, Nowell PC, Croce CM, et al. Cloning of ALL-1, the locus involved in leukemias with the t(4;11)(q21;q23), t(9;11)(p22;q23), and t(11;19)(q23;p13) chromosome translocations. Cancer Res. 1991 Dec 15;51(24):6712–6714. [PubMed]
  • Ziemin-van der Poel S, McCabe NR, Gill HJ, Espinosa R, 3rd, Patel Y, Harden A, Rubinelli P, Smith SD, LeBeau MM, Rowley JD, et al. Identification of a gene, MLL, that spans the breakpoint in 11q23 translocations associated with human leukemias. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10735–10739. [PubMed]
  • Cherif D, Der-Sarkissian H, Derré J, Tokino T, Nakamura Y, Berger R. The 11q23 breakpoint in acute leukemia with t(11;19)(q23;p13) is distal to those of t(4;11), t(6;11) and t(9;11). Genes Chromosomes Cancer. 1992 Mar;4(2):107–112. [PubMed]
  • Akao Y, Seto M, Takahashi T, Saito M, Utsumi KR, Nakazawa S, Ueda R. Rearrangements on chromosome 11q23 in hematopoietic tumor-associated t(11;14) and t(11;19) translocations. Cancer Res. 1991 Dec 15;51(24):6708–6711. [PubMed]
  • Lu D, Yunis JJ. Cloning, expression and localization of an RNA helicase gene from a human lymphoid cell line with chromosomal breakpoint 11q23.3. Nucleic Acids Res. 1992 Apr 25;20(8):1967–1972. [PMC free article] [PubMed]

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