The t(8;21) fusion product, AML-1-ETO, associates with C/EBP-α, inhibits C/EBP-α-dependent transcription, and blocks granulocytic differentiation

Molecular and Cellular Biology

Volumn 18, Issue 1, 1998, Pages 322-333

  Westendorf, Jennifer J ^a,b   Yamamoto, Cindy M ^c   Lenny, Noel ^d   Downing, James R ^d   Selsted, Michael E ^c   Hiebert, Scott W ^a,b  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b VANDERBILT INGRAM CANCER CENTER   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DEFENSIN; DNA; GRANULOCYTE COLONY STIMULATING FACTOR; MYOSIN HEAVY CHAIN; NUCLEAR PROTEIN; TRANSCRIPTION FACTOR;

ANIMAL CELL; ARTICLE; CARBOXY TERMINAL SEQUENCE; CELL DIFFERENTIATION; CERCOPITHECIDAE; CONTROLLED STUDY; DELETION MUTANT; DNA BINDING; GENETIC TRANSCRIPTION; GRANULOCYTE; HUMAN; HUMAN CELL; IMMUNOPRECIPITATION; LEUKEMOGENESIS; NONHUMAN; PRIORITY JOURNAL;

ANIMALIA; CERCOPITHECIDAE; MURINAE;

EID: 0031972701     PISSN: 02707306     EISSN: None     Source Type: Journal    
DOI: 10.1128/mcb.18.1.322     Document Type: Article

References (80)

1. Bae, S. C., E. Takahashi, Y. W. Zhang, E. Ogawa, K. Shigesada, Y. Namba, M. Satake, and Y. Ito. 1995. Cloning, mapping and expression of PEBP2 alpha C, a third gene encoding the mammalian Runt domain. Gene 159: 245-248.
2. Banaiee, N., et al. Unpublished data.
3. Birkenmeier, E. H., B. Gwynn, S. Howard, J. Jerry, J. I. Gordon, W. H. Landschulz, and S. L. McKnight. 1989. Tissue-specific expression, developmental regulation, and genetic mapping of the gene encoding CCAAT/ enhancer binding protein. Genes Dev. 3:1146-1156.
4. Cameron, S., D. S. Taylor, E. C. TePas, N. A. Speck, and B. Mathey-Prevot. 1994. Identification of a critical regulatory site in the human interleukin-3 promoter by in vivo footprinting. Blood 83:2851-2859.
5. Cao, Z., R. M. Umek, and S. L. McKnight. 1991. Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells. Genes Dev. 5:1538-1552.
6. Castilla, L. H., C. Wijmenga, Q. Wang, T. Stacy, N. A. Speck, M. Eckhaus, M. Marin-Padilla, F. S. Collins, A. Wynshaw-Boris, and P. P. Liu. 1996. Failure of embryonic hematopoiesis and lethal hemorrhages in mouse embryos heterozygous for a knocked-in leukemia gene CBFB-MYH11. Cell 87:687-696.
7. Daher, K. A., R. I. Lehrer, T. Ganz, and M. Kronenberg. 1988. Isolation and characterization of human defensin cDNA clones. Proc. Natl. Acad. Sci. USA 85:7327-7331.
8. Downing, J. R., D. R. Head, A. M. Curcio-Brint, M. G. Hulshof, T. A. Motroni, S. C. Raimondi, A. J. Carroll, H. A. Drabkin, C. Willman, K. S. Theil, et al. 1993. An AML1/ETO fusion transcript is consistently detected by RNA-based polymerase chain reaction in acute myelogenous leukemia containing the (8;21)(q22;q22) translocation. Blood 81:2860-2865.
9. Erickson, P., J. Gao, K. S. Chang, T. Look, E. Whisenant, S. Raimondi, R. Lasher, J. Trujillo, J. Rowley, and H. Drabkin. 1992. Identification of breakpoints in t(8;21) acute myelogenous leukemia and isolation of a fusion transcript, AML1/ETO, with similarity to Drosophila segmentation gene, runt. Blood 80:1825-1831.
10. Erickson, P. F., G. Dessev, R. S. Lasher, G. Philips, M. Robinson, and H. A. Drabkin. 1996. ETO and AML1 phosphoproteins are expressed in CD34+ hematopoietic progenitors: implications for t(8;21) leukemogenesis and monitoring residual disease. Blood 88:1813-1823.
11. Erickson, P. F., M. Robinson, G. Owens, and H. A. Drabkin. 1994. The ETO portion of acute myeloid leukemia 1(8:21) fusion transcript encodes a highly evolutionarily conserved, putative transcription factor. Cancer Res. 54:1782-1786.
12. Fears, S., M. Gavin, D. E. Zhang, C. Hetherington, Y. Ben-David, J. D. Rowley, and G. Nucifora. 1997. Functional characterization of ETV6 and ETV6/CBFA2 in the regulation of the MCSFR proximal promoter. Proc. Natl. Acad. Sci. USA 94:1949-1954.
13. Feinstein, P. G., K. Kornfeld, D. S. Hogness, and R. S. Mann. 1995. Identification of homeotic target genes in Drosophila melanogaster including nervy, a proto-oncogene homologue. Genetics 140:573-586.
14. Frank, R., J. Zhang, H. Uchida, S. Meyers, S. W. Hiebert, and S. D. Nimer. 1995. The AML1/ETO fusion protein blocks transactivation of the GM-CSF promoter by AML1B. Oncogene 11:2667-2674.
15. Ganz, T., M. E. Selsted, and R. I. Lehrer. 1990. Defensins. Eur. J. Haematol. 44:1-8.
16. Golub, T. R., G. F. Barker, S. K. Bohlander, S. W. Hiebert, D. C. Ward, P. Bray-Ward, E. Morgan, S. C. Raimondi, J. D. Rowley, and D. G. Gilliland. 1995. Fusion of the TEL gene on 12p13 to the AML1 gene on 21q22 in acute lymphoblastic leukemia. Proc. Natl. Acad. Sci. USA 92:4917-4921.
17. Golub, T. R., G. F. Barker, M. Lovett, and D. G. Gilliland. 1994. Fusion of PDGF receptor beta to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation. Cell 77:307-316.
18. Gorman, C. M., L. F. Moffat, and B. H. Howard. 1982. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol. Cell. Biol. 2:1044-1051.
19. Gottschalk, L. R., and J. M. Leiden. 1990. Identification and functional characterization of the human T-cell receptor beta gene transcriptional enhancer: common nuclear proteins interact with the transcriptional regulatory elements of the T-cell receptor alpha and beta genes. Mol. Cell. Biol. 10: 5486-5495.
20. Gross, C. T., and W. McGinnis. 1996. DEAF-1, a novel protein that binds an essential region in a Deformed response element. EMBO J. 15:1961-1970.
21. Hiebert, S. W., M. Blake, J. Azizkhan, and J. R. Nevins. 1991. Role of E2F transcription factor in E1A-mediated trans activation of cellular genes. J. Virol. 65:3547-3552.
22. Hiebert, S. W., S. P. Chellappan, J. M. Horowitz, and J. R. Nevins. 1992. The interaction of RB with E2F coincides with an inhibition of the transcriptional activity of E2F. Genes Dev. 6:177-185.
23. Hiebert, S. W., and S. Meyers. Unpublished data.
24. Hiebert, S. W., G. Packham, D. K. Strom, R. Haffner, M. Oren, G. Zambetti, and J. L. Cleveland. 1995. E2F-1:DP-1 induces p53 and overrides survival factors to trigger apoptosis. Mol. Cell. Biol. 15:6864-6874.
25. Hiebert, S. W., W. Sun, J. N. Davis, T. Golub, S. Shurtleff, A. Buijs, J. R. Downing, G. Grosveld, M. F. Roussell, D. G. Gilliland, N. Lenny, and S. Meyers. 1996. The t(12;21) translocation converts AML-1B from an activator to a repressor of transcription. Mol. Cell. Biol. 16:1349-1355.
26. Hohaus, S., M. S. Petrovick, M. T. Voso, Z. Sun, D. E. Zhang, and D. G. Tenen. 1995. PU.1 (Spi-1) and C/EBP alpha regulate expression of the granulocyte-macrophage colony-stimulating factor receptor alpha gene. Mol. Cell. Biol. 15:5830-5845.
27. Hsiang, Y. H., D. Spencer, S. Wang, N. A. Speck, and D. H. Raulet. 1993. The role of viral enhancer "core" motif-related sequences in regulating T cell receptor-gamma and -delta gene expression. J. Immunol. 150:3905-3916.
28. Johnson, P. F., W. H. Landschulz, B. J. Graves, and S. L. McKnight. 1987. Identification of a rat liver nuclear protein that binds to the enhancer core element of three animal viruses. Genes Dev. 1:133-146.
29. Klampfer, L., J. Zhang, A. O. Zelenetz, H. Uchida, and S. D. Nimer. 1996. The AML1/ETO fusion protein activates transcription of BCL-2. Proc. Natl. Acad. Sci. USA 93:14059-14064.
30. Lehrer, R. I., T. Ganz, and M. E. Selsted. 1991. Defensins: endogenous antibiotic peptides of animal cells. Cell 64:229-230.
31. Lehrer, R. I., A. K. Lichtenstein, and T. Ganz. 1993. Defensins: antimicrobial and cytotoxic peptides of mammalian cells. Annu. Rev. Immunol. 11:105-128.
32. Lenny, N., S. Meyers, and S. W. Hiebert. 1995. Functional domains of the t(8;21) fusion protein, AML-1/ETO. Oncogene 11:1761-1769.
33. Levanon, D., V. Negreanu, Y. Bernstein, I. Bar-Am, L. Avivi, and Y. Groner. 1994. AML1, AML2, and AML3, the human members of the runt domain gene-family: cDNA structure, expression, and chromosomal localization. Genomics 23:425-432.
34. Linzmeier, R., D. Michaelson, L. Liu, and T. Ganz. 1993. The structure of neutrophil defensin genes. FEBS Lett. 326:299-300.
35. Liu, P., S. A. Tarle, A. Hajra, D. F. Claxton, P. Marlton, M. Freedman, M. J. Siciliano, and F. S. Collins. 1993. Fusion between transcription factor CBF beta/PEBP2 beta and a myosin heavy chain in acute myeloid leukemia. Science 261:1041-1044.
36. Meyers, S., J. R. Downing, and S. W. Hiebert. 1993. Identification of AML-1 and the (8;21) translocation protein (AML-1/ETO) as sequence-specific DNA-binding proteins: the runt homology domain is required for DNA binding and protein-protein interactions. Mol. Cell. Biol. 13:6336-6345.
37. Meyers, S., and S. W. Hiebert. 1995. Indirect and direct disruption of transcriptional regulation in cancer: E2F and AML-1. Crit. Rev. Eukaryotic Gene Expr. 5:365-383.
38. Meyers, S., N. Lenny, and S. W. Hiebert. 1995. The t(8;21) fusion protein interferes with AML-1B-dependent transcriptional activation. Mol. Cell. Biol. 15:1974-1982.
39. Meyers, S., N. Lenny, W. Sun, and S. W. Hiebert. 1996. AML-2 is a potential target for transcriptional regulation by the t(8;21) and t(12;21) fusion proteins in acute leukemia. Oncogene 13:303-312.
40. Mitani, K., S. Ogawa, T. Tanaka, H. Miyoshi, M. Kurokawa, H. Mano, Y. Yazaki, M. Ohki, and H. Hirai. 1994. Generation of the AML1-EVI-1 fusion gene in the t(3;21)(q2b;q22) causes blastic crisis in chronic myelocytic leukemia. EMBO J. 13:504-510.
41. Miyoshi, H., T. Kozu, K. Shimizu, K. Enomoto, N. Maseki, Y. Kaneko, N. Kamada, and M. Ohki. 1993. The t(8;21) translocation in acute myeloid leukemia results in production of an AML1-MTG8 fusion transcript. EMBO J. 12:2715-2721.
42. Miyoshi, H., K. Shimizu, T. Kozu, N. Maseki, Y. Kaneko, and M. Ohki. 1991. t(8;21) breakpoints on chromosome 21 in acute myeloid leukemia are clustered within a limited region of a single gene, AML1. Proc. Natl. Acad. Sci. USA 88:10431-10434.
43. Morishita, K., D. S. Parker, M. L. Mucenski, N. A. Jenkins, N. G. Copeland, and J. N. Ihle. 1988. Retroviral activation of a novel gene encoding a zinc finger protein in IL-3-dependent myeloid leukemia cell lines. Cell 54:831-840.
44. Nisson, P. E., P. C. Watkins, and N. Sacchi. 1992. Transcriptionally active chimeric gene derived from the fusion of the AML1 gene and a novel gene on chromosome 8 in t(8;21) leukemic cells. Cancer Genet. Cytogenet. 63: 81-88.
45. Nuchprayoon, I., S. Meyers, L. M. Scott, J. Suzow, S. Hiebert, and A. D. Friedman. 1994. PEBP2/CBF, the murine homolog of the human myeloid AML1 and PEBP2 beta/CBF beta proto-oncoproteins, regulates the murine myeloperoxidase and neutrophil elastase genes in immature myeloid cells. Mol. Cell. Biol. 14:5558-5568.
46. Nucifora, G., C. R. Begy, P. Erickson, H. A. Drabkin, and J. D. Rowley. 1993. The 3;21 translocation in myelodysplasia results in a fusion transcript between the AML1 gene and the gene for EAP, a highly conserved protein associated with the Epstein-Barr virus small RNA EBER 1. Proc. Natl. Acad. Sci. USA 90:7784-7788.
47. Nucifora, G., C. R. Begy, H. Kobayashi, D. Roulston, D. Claxton, J. Pedersen-Bjergaard, E. Parganas, J. N. Ihle, and J. D. Rowley. 1994. Consistent intergenic splicing and production of multiple transcripts between AML1 at 21q22 and unrelated genes at 3q26 in (3;21)(q26;q22) translocations. Proc. Natl. Acad. Sci. USA 91:4004-4008.
48. Nucifora, G., D. J. Birn, P. Erickson, J. Gao, M. M. LeBeau, H. A. Drabkin, and J. D. Rowley. 1993. Detection of DNA rearrangements in the AML1 and ETO loci and of an AML1/ETO fusion mRNA in patients with t(8;21) acute myeloid leukemia. Blood 81:883-888.
49. Nucifora, G., D. J. Birn, R. D. Espinosa, P. Erickson, M. M. LeBeau, D. Roulston, T. W. McKeithan, H. Drabkin, and J. D. Rowley. 1993. Involvement of the AML1 gene in the t(3;21) in therapy-related leukemia and in chronic myeloid leukemia in blast crisis. Blood 81:2728-2734.
50. Oelgeschlager, M., I. Nuchprayoon, B. Luscher, and A. D. Friedman. 1996. C/EBP, c-Myb, and PU.1 cooperate to regulate the neutrophil elastase promoter. Mol. Cell. Biol. 16:4717-4725.
51. Ogawa, E., M. Maruyama, H. Kagoshima, M. Inuzuka, J. Lu, M. Satake, K. Shigesada, and Y. Ito. 1993. PEBP2/PEA2 represents a family of transcription factors homologous to the products of the Drosophila runt gene and the human AML1 gene. Proc. Natl. Acad. Sci. USA 90:6859-6863.
52. Okuda, T., J. van Deursen, S. W. Hiebert, G. Grosveld, and J. R. Downing. 1996. AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis. Cell 84:321-330.
53. Owens, G. P., W. E. Hahn, and J. J. Cohen. 1991. Identification of mRNAs associated with programmed cell death in immature thymocytes. Mol. Cell. Biol. 11:4177-1188.
54. Petrovick, M. S., S. W. Hiebert, A. D. Friedman, C. J. Hetherington, D. G. Tenen, and D. E. Zhang. Multiple functional domains of AML1: PU.1 and C/EBP-α cooperate with different regions of AML1. Submitted for publication.
55. Redondo, J. M., J. L. Pfohl, and M. S. Krangel. 1991. Identification of an essential site for transcriptional activation within the human T-cell receptor delta enhancer. Mol. Cell. Biol. 11:5671-5680.
56. Rhoades, K. L., C. J. Hetherington, J. D. Rowley, S. W. Hiebert, G. Nucifora, D. G. Tenen, and D. E. Zhang. 1996. Synergistic up-regulation of the myeloid-specific promoter for the macrophage colony-stimulating factor receptor by AML1 and the t(8;21) fusion protein may contribute to leukemogenesis. Proc. Natl. Acad. Sci. USA 93:11895-11900.
57. Romana, S. P., M. Mauchauffe, M. Le Coniat, I. Chumakov, D. Le Paslier, R. Berger, and O. A. Bernard. 1995. The t(12:21) of acute lymphoblastic leukemia results in a tel-AML1 gene fusion. Blood 85:3662-3670.
58. Romana, S. P., H. Poirel, M. Leconiat, M. A. Flexor, M. Mauchauffe, P. Jonveaux, E. A. Macintyre, R. Berger, and O. A. Bernard. 1995. High frequency of t(12;21) in childhood B-lineage acute lymphoblastic leukemia. Blood 86:4263-4269.
59. Rubin, C. M., R. A. Larson, J. Anastasi, J. N. Winter, M. Thangavelu, J. W. Vardiman, J. D. Rowley, and M. M. Le Beau. 1990. t(3;21)(q2h;q22): a recurring chromosomal abnormality in therapy-related myelodysplastic syndrome and acute myeloid leukemia. Blood 76:2594-2598.
60. Sacchi, N., P. E. Nisson, P. C. Watkins, F. Faustinella, J. Wijsman, and A. Hagemeijer. 1994. AML1 fusion transcripts in t(3;21) positive leukemia: evidence of molecular heterogeneity and usage of splicing sites frequently involved in the generation of normal AML1 transcripts. Genes Chromosomes Cancer 11:226-236.
61. Sawyers, C. L., C. T. Denny, and O. N. Witte. 1991. Leukemia and the disruption of normal hematopoiesis. Cell 64:337-350.
62. Scott, L. M., C. I. Civin, P. Rorth, and A. D. Friedman. 1992. A novel temporal expression pattern of three C/EBP family members in differentiating myelomonocytic cells. Blood 80:1725-1735.
63. Shurtleff, S. A., A. Buijs, F. G. Behm, J. E. Rubnitz, S. C. Raimondi, M. L. Hancock, G. C. Chan, C. H. Pui, G. Grosveld, and J. R. Downing. 1995. TEL/AML1 fusion resulting from a cryptic t(12;21) is the most common genetic lesion in pediatric ALL and defines a subgroup of patients with an excellent prognosis. Leukemia 9:1985-1989.
64. Shurtleff, S. A., S. Meyers, S. W. Hiebert, S. C. Raimondi, D. R. Head, C. L. Willman, S. Wolman, M. L. Slovak, A. J. Carroll, F. Behm, et al. 1995. Heterogeneity in CBF beta/MYH11 fusion messages encoded by the inv(16)(p13q22) and the t(16;16)(p13;q22) in acute myelogenous leukemia. Blood 85:3695-3703.
65. Smith, L. T., S. Hohaus, D. A. Gonzalez, S. E. Dziennis, and D. G. Tenen. 1996. PU.1 (Spi-1) and C/EBP alpha regulate the granulocyte colony-stimulating factor receptor promoter in myeloid cells. Blood 88:1234-1247.
66. Suzow, J., and A. D. Friedman. 1993. The murine myeloperoxidase promoter contains several functional elements, one of which binds a cell type-restricted transcription factor, myeloid nuclear factor 1 (MyNF1). Mol. Cell. Biol. 13:2141-2151.
67. Tanaka, T., M. Kurokawa, K. Ueki, K. Tanaka, Y. Imai, K. Mitani, K. Okazaki, N. Sagata, Y. Yazaki, Y. Shibata, T. Kadowaki, and H. Hirai. 1996. The extracellular signal-regulated kinase pathway phosphorylates AML1, an acute myeloid leukemia gene product, and potentially regulates its transactivation ability. Mol. Cell. Biol. 16:3967-3979.
68. Uchida, H., J. Zhang, and S. D. Nimer. 1997. AML1A and AML1B can transactivate the human IL-3 promoter. J. Immunol. 158:2251-2258.
69. Wang, Q., T. Stacy, M. Binder, M. Marin-Padilla, A. H. Sharpe, and N. A. Speck. 1996. Disruption of the Cbfa2 gene causes necrosis and hemorrhaging in the central nervous system and blocks definitive hematopoiesis. Proc. Natl. Acad. Sci. USA 93:3444-3449.
70. Wang, Q., T. Stacy, J. D. Miller, A. F. Lewis, T. L. Gu, X. Huang, J. H. Bushweller, J. C. Bories, F. W. Alt, G. Ryan, P. P. Liu, A. Wynshaw-Boris, M. Binder, M. Marin-Padilla, A. H. Sharpe, and N. A. Speck. 1996. The CBF-beta subunit is essential for CBFalpha2 (AML1) function in vivo. Cell 87: 697-708.
71. Wang, S., Q. Wang, B. E. Crute, I. N. Melnikova, S. R. Keller, and N. A. Speck. 1993. Cloning and characterization of subunits of the T-cell receptor and murine leukemia virus enhancer core-binding factor. Mol. Cell. Biol. 13:3324-3339.
72. Westendorf, J. J., and S. W. Hiebert. Unpublished data.
73. Yamamoto, C. M., et al. Unpublished data.
74. Yergeau, D. A., C. J. Hetherington, Q. Wang, P. Zhang, A. H. Sharpe, M. Binder, M. Marin-Padilla, D. G. Tenen, N. A. Speck, and D. E. Zhang. 1997. Embryonic lethality and impairment of haematopoiesis in mice heterozygous for an AML1-ETO fusion gene. Nat. Genet. 15:303-306.
75. Yount, N. Y., M. S. Wang, J. Yuan, N. Banaiee, A. J. Ouellette, and M. E. Selsted. 1995. Rat neutrophil dcfensins. Precursor structures and expression during neutrophilic myelopoiesis. J. Immunol. 155:4476-4484.
76. Zeng, C., A. J. van Wijnen, J. L. Stein, S. Meyers, W. Sun, L. Shopland, J. B. Lawrence, S. Penman, J. B. Lian, G. S. Stein, and S. W. Hiebert. 1997. Identification of a nuclear matrix targeting signal in the leukemia and bone-related AML/CBF-alpha transcription factors. Proc. Natl. Acad. Sci. USA 94:6746-6751.
77. Zhang, D.-E., K. Fujioka, C. J. Hetherington, L. H. Shapiro, H.-M. Chen, A. T. Look, and D. G. Tenen. 1994. Identification of a region which directs the monocytic activity of the colony-stimulating factor 1 (macrophage colony-stimulating factor) receptor promoter and binds PEBP2/CBF (AML1). Mol. Cell. Biol. 14:8085-8095.
78. Zhang, D.-E., C. J. Hetherington, S. Meyers, K. L. Rhoades, C. J. Larson, H.-M. Chen, S. W. Hiebert, and D. G. Tenen. 1996. CCAAT enhancer-binding protein (C/EBP) and AML1 (CBFα2) synergistically activate the macrophage colony-stimulating factor receptor promoter. Mol. Cell. Biol. 16:1231-1240.
79. Zhang, D. E., S. Hohaus, M. T. Voso, H. M. Chen, L. T. Smith, C. J. Hetherington, and D. G. Tenen. 1996. Function of PU.1 (Spi-1), C/EBP, and AML1 in early myelopoiesis: regulation of multiple myeloid CSF receptor promoters. Curr. Top. Microbiol. Immunol. 211:137-147.
80. Zhang, D. E., P. Zhang, N. D. Wang, C. J. Hetherington, G. J. Darlington, and D. G. Tenen. 1997. Absence of granulocyte colony-stimulating factor signaling and neutrophil development in CCAAT enhancer binding protein alpha-deficient mice. Proc. Natl. Acad. Sci. USA 94:569-574.