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Proc Natl Acad Sci U S A. Dec 1, 1991; 88(23): 10431–10434.

t(8;21) breakpoints on chromosome 21 in acute myeloid leukemia are clustered within a limited region of a single gene, AML1.


The t(8;21)(q22;q22) translocation is a non-random chromosomal abnormality frequently found in patients with acute myeloid leukemia (AML) with maturation (M2 subtype). We report here the cloning of a gene, named AML1, on chromosome 21 that was found to be rearranged in the leukemic cell DNAs from t(8;21) AML patients. The breakpoints in 16 out of 21 patients were clustered within a limited region of AML1, and detailed analysis in 3 patients revealed that the breakpoints occurred in the same intron of the gene. Sequencing of cDNA clones identified a long open reading frame encoding a 250-amino acid protein. Northern blot analysis detected four constant mRNA species in t(8;21) leukemic and normal cells; the largest species was more abundant in the leukemic cells than in normal cells. In addition, two mRNA species limited to the leukemic cells were found. These findings indicate that the AML1 gene may be involved in neoplastic transformation of AML with the t(8;21) translocation.

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  • 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]
  • 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]
  • Alcalay M, Zangrilli D, Pandolfi PP, Longo L, Mencarelli A, Giacomucci A, Rocchi M, Biondi A, Rambaldi A, Lo Coco F, et al. 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. [PMC free article] [PubMed]
  • von Lindern M, Poustka A, Lerach H, Grosveld G. The (6;9) chromosome translocation, associated with a specific subtype of acute nonlymphocytic leukemia, leads to aberrant transcription of a target gene on 9q34. Mol Cell Biol. 1990 Aug;10(8):4016–4026. [PMC free article] [PubMed]
  • Rowley JD. Recurring chromosome abnormalities in leukemia and lymphoma. Semin Hematol. 1990 Apr;27(2):122–136. [PubMed]
  • Johansson B, Mertens F, Mitelman F. Geographic heterogeneity of neoplasia-associated chromosome aberrations. Genes Chromosomes Cancer. 1991 Jan;3(1):1–7. [PubMed]
  • Kaneko Y, Kimpara H, Kawai S, Fujimoto T. 8;21 chromosome translocation in eosinophilic leukemia. Cancer Genet Cytogenet. 1983 Jun;9(2):181–183. [PubMed]
  • Abe R, Umezu H, Uchida T, Kariyone S, Maseki N, Kaneko Y, Sakurai M. Myeloblastoma with an 8;21 chromosome translocation in acute myeloblastic leukemia. Cancer. 1986 Sep 15;58(6):1260–1264. [PubMed]
  • Drabkin HA, Diaz M, Bradley CM, Le Beau MM, Rowley JD, Patterson D. Isolation and analysis of the 21q+ chromosome in the acute myelogenous leukemia 8;21 translocation: evidence that c-mos is not translocated. Proc Natl Acad Sci U S A. 1985 Jan;82(2):464–468. [PMC free article] [PubMed]
  • Sacchi N, Watson DK, Guerts van Kessel AH, Hagemeijer A, Kersey J, Drabkin HD, Patterson D, Papas TS. Hu-ets-1 and Hu-ets-2 genes are transposed in acute leukemias with (4;11) and (8;21) translocations. Science. 1986 Jan 24;231(4736):379–382. [PubMed]
  • Rao VN, Papas TS, Reddy ES. erg, a human ets-related gene on chromosome 21: alternative splicing, polyadenylation, and translation. Science. 1987 Aug 7;237(4815):635–639. [PubMed]
  • Shimizu K, Ichikawa H, Miyoshi H, Ohki M, Kobayashi H, Maseki N, Kaneko Y. Molecular assignment of a translocation breakpoint in acute myeloid leukemia with t(8;21). Genes Chromosomes Cancer. 1991 May;3(3):163–167. [PubMed]
  • Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. [PubMed]
  • Kozak M. An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res. 1987 Oct 26;15(20):8125–8148. [PMC free article] [PubMed]
  • Möller W, Amons R. Phosphate-binding sequences in nucleotide-binding proteins. FEBS Lett. 1985 Jul 1;186(1):1–7. [PubMed]
  • Asou H, Tashiro S, Hamamoto K, Otsuji A, Kita K, Kamada N. Establishment of a human acute myeloid leukemia cell line (Kasumi-1) with 8;21 chromosome translocation. Blood. 1991 May 1;77(9):2031–2036. [PubMed]
  • Shaw G, Kamen R. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell. 1986 Aug 29;46(5):659–667. [PubMed]
  • Cory S. Activation of cellular oncogenes in hemopoietic cells by chromosome translocation. Adv Cancer Res. 1986;47:189–234. [PubMed]
  • Croce CM, Erikson J, Haluska FG, Finger LR, Showe LC, Tsujimoto Y. Molecular genetics of human B- and T-cell neoplasia. Cold Spring Harb Symp Quant Biol. 1986;51(Pt 2):891–898. [PubMed]
  • Kurzrock R, Gutterman JU, Talpaz M. The molecular genetics of Philadelphia chromosome-positive leukemias. N Engl J Med. 1988 Oct 13;319(15):990–998. [PubMed]
  • Rabbitts TH, Boehm T, Mengle-Gaw L. Chromosomal abnormalities in lymphoid tumours: mechanism and role in tumour pathogenesis. Trends Genet. 1988 Nov;4(11):300–304. [PubMed]
  • Sawyers CL, Denny CT, Witte ON. Leukemia and the disruption of normal hematopoiesis. Cell. 1991 Jan 25;64(2):337–350. [PubMed]

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