The t(8;21) fusion protein, AML1-ETO, specifically represses the transcription of the p14ARF tumor suppressor in acute myeloid leukemia

Nature Medicine

Volumn 8, Issue 7, 2002, Pages 743-750

  Linggi, Bryan ^a   Müller Tidow, Carsten ^b   van de Locht, Louis ^c   Hu, Ming ^d   Nip, John ^a   Serve, Hubert ^b   Berdel, Wolfgang E ^b   van der Reijden, Bert ^c   Quelle, Dawn E ^e   Rowley, Janet D ^f   Cleveland, John ^g   Jansen, Joop H ^c   Pandolfi, Pier Paolo ^d   Hiebert, Scott W ^a  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF MÜNSTER   (Germany)

^c RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^d Department of Obstetrics Gynecology   (United States)

^e UNIVERSITY OF IOWA   (United States)

^f UNIVERSITY OF CHICAGO   (United States)

^g UNIVERSITY OF TENNESSEE HEALTH SCIENCE CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DNA; HYBRID PROTEIN; MESSENGER RNA; PROTEIN P14; PROTEIN P53; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR ETO; TRANSCRIPTION FACTOR RUNX1; UNCLASSIFIED DRUG;

ACUTE GRANULOCYTIC LEUKEMIA; ARTICLE; BINDING SITE; CELL AGING; CELL IMMORTALIZATION; CELL LEVEL; CELL TYPE; CHROMATIN; CHROMOSOME TRANSLOCATION 21; CHROMOSOME TRANSLOCATION 8; CONTROLLED STUDY; DISEASE ASSOCIATION; DNA BINDING; GENE MUTATION; GENE REPRESSION; GENETIC TRANSCRIPTION; HEMATOPOIETIC STEM CELL; HUMAN; HUMAN CELL; IMMUNOPRECIPITATION; INHIBITION KINETICS; ONCOGENE; PHENOTYPE; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN ANALYSIS; PROTEIN EXPRESSION; SENESCENCE; STIMULATION;

ANTIGENS, CD; ANTIGENS, CD4; CHROMOSOMES, HUMAN, PAIR 21; CHROMOSOMES, HUMAN, PAIR 8; CORE BINDING FACTOR ALPHA 2 SUBUNIT; GENE EXPRESSION REGULATION, NEOPLASTIC; GENES, REPORTER; GENES, TUMOR SUPPRESSOR; HEMATOPOIETIC STEM CELLS; HUMANS; K562 CELLS; LEUKEMIA, MYELOCYTIC, ACUTE; ONCOGENE PROTEINS, FUSION; PLASMIDS; REPRESSOR PROTEINS; TRANSCRIPTION FACTORS; TRANSCRIPTION, GENETIC; TRANSLOCATION, GENETIC; TUMOR CELLS, CULTURED; TUMOR SUPPRESSOR PROTEIN P14ARF;

EID: 18444392071     PISSN: 10788956     EISSN: None     Source Type: Journal    
DOI: 10.1038/nm726     Document Type: Article

References (44)

1. The role of chromosome translocations in leukemogenesis
2. The role of TEL fusion genes in pediatric leukemias
3. Biallelic and heterozygous point mutations in the runt domain of the AML1/PEBP 2alphaB gene associated with myeloblastic leukemias
4. Haploinsufficiency of CBFA 2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia
5. Sequence specificity of the corebinding factor
6. 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
7. ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with multiple histone deacetylases and binds mSin 3A through its oligomerization domain
8. AML1 and the AML1-ETO fusion protein in the pathogenesis of t(8;21) AML
9. Analysis of the role of AML1-ETO in leukemogenesis, using an inducible transgenic mouse model
10. Expression of a knocked-in AML1-ETO leukemia gene inhibits the establishment of normal definitive hematopoiesis and directly generates dysplastic hematopoietic progenitors
11. The AML1-ETO fusion protein promotes the expansion of human hematopoietic stem cells
12. p14ARF links the tumour suppressors RB and p53
13. Inhibition of v-Abl transformation by p53 and p19ARF
14. E1A signaling to p53 involves the p19(ARF) tumor suppressor
15. p19ARF links the tumour suppressor p53 to Ras
16. Myc signaling via the ARF tumor suppressor regulates p53-dependent apoptosis and immortalization
17. The Ink4a tumor suppressor gene product, p19Arf, interacts with MDM2 and neutralizes MDM2's inhibition of p53
18. ARF promotes MDM2 degradation and stabilizes p53: ARF-INK 4a locus deletion impairs both the Rb and p53 tumor suppression pathways
19. p53 alteration is a common event in the spontaneous immortalization of primary BALB/c murine embryo fibroblasts
20. Tumor suppression at the mouse INK 4a locus mediated by the alternative reading frame product p19ARF
21. Cancer cell cycles
22. The INK4A/ARF locus and its two gene products
23. Loss of p 16Ink4a with retention of p19Arf predisposes mice to tumorigenesis
24. Loss of p 16Ink4a confers susceptibility to metastatic melanoma in mice
25. Regulation of a senescence checkpoint response by the E2F1 transcription factor and p14(ARF) tumor suppressor
26. Mutations in human ARF exon 2 disrupt its nucleolar localization and impair its ability to block nuclear export of MDM2 and p53
27. p53 in hematologic malignancies
28. Overexpression of the MDM2 gene by childhood acute lymphoblastic leukemia cells expressing the wild-type p53 gene
29. The t(8;21) translocation is not consistently associated with high Bcl- 2 expression in de novo acute myeloid leukemias of adults
30. p16ink4a gene and hematological malignancies
31. The human ARF cell cycle regulatory gene promoter is a CpG island which can be silenced by DNA methylation and down-regulated by wild-type p53
32. Functional domains of the t(8;21) fusion protein, AML-1/ETO
33. The alternative product from the human CDKN2A locus, p14(ARF), participates in a regulatory feedback loop with p53 and MDM2
34. A biomarker that identifies senescent human cells in culture and in aging skin in vivo
35. The p16INK4a/CDKN 2A tumor suppressor and its relatives
36. Expression of pl 61NK4A and p14ARF in hematological malignancies
37. Isolation of a cDNA encoding CD 33, a differentiation antigen of myeloid progenitor cells
38. Disruption of the ARF-Mdm2-p53 tumor suppressor pathway in Myc-induced lymphomagenesis
39. Participation of p53 cellular tumour antigen in transformation of normal embryonic cells
40. p53-independent functions of the p19(ARF) tumor suppressor
41. The oncogene and Polycomb-group gene bmi- 1 regulates cell proliferation and senescence through the ink4a locus
42. Senescence bypass screen identifies TBX2, which represses Cdkn2a (p19(ARF)) and is amplified in a subset of human breast cancers
43. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
44. Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription