Targeting of AML1-ETO in t(8;21) leukemia by oridonin generates a tumor suppressor-like protein

Science Translational Medicine

Volumn 4, Issue 127, 2012, Pages

  Zhen, Tao ^a   Wu, Chuan Feng ^a   Liu, Ping ^a   Wu, Hai Yan ^b   Zhou, Guang Biao ^c   Lu, Ying ^a   Liu, Jian Xiang ^a   Liang, Yang ^a   Li, Keqin Kathy ^a   Wang, Yue Ying ^a   Xie, Yin Yin ^a   He, Miao Miao ^a   Cao, Huang Ming ^a   Zhang, Wei Na ^a   Chen, Li Min ^a,d   Petrie, Kevin ^e   Chen, Sai Juan ^a,b,e   Chen, Zhu ^a,b,e  

^a SHANGHAI JIAO TONG UNIVERSITY SCHOOL OF MEDICINE   (China)

^b Shanghai Jiao Tong University   (China)

^c INSTITUTE OF ZOOLOGY   (China)

^d SHANGHAI INSTITUTE OF MATERIA MEDICA   (China)

^e SHANGHAI SECOND MEDICAL UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

ACUTE MYELOID LEUKEMIA 1 ETO FUSION PROTEIN; ASPARTIC ACID; CASPASE 3; GLUTATHIONE; GRANULOCYTE COLONY STIMULATING FACTOR; ONCOPROTEIN; ORIDONIN; REACTIVE OXYGEN METABOLITE; RETINOIC ACID; STEM CELL FACTOR; THIOREDOXIN; THIOREDOXIN REDUCTASE; UNCLASSIFIED DRUG; AML1 ETO FUSION PROTEIN, HUMAN; AML1-ETO FUSION PROTEIN, HUMAN; KAURANE DERIVATIVE; TRANSCRIPTION FACTOR RUNX1; TUMOR SUPPRESSOR PROTEIN;

ACUTE GRANULOCYTIC LEUKEMIA; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER COMBINATION CHEMOTHERAPY; CANCER INHIBITION; CANCER SURVIVAL; CONTROLLED STUDY; DRUG CYTOTOXICITY; DRUG EFFECT; DRUG MECHANISM; DRUG PROTEIN BINDING; DRUG SAFETY; ENZYME ACTIVATION; IN VITRO STUDY; IN VIVO STUDY; LEUKEMIA CELL LINE; LEUKEMOGENESIS; MAXIMUM PLASMA CONCENTRATION; MOLECULARLY TARGETED THERAPY; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN CLEAVAGE; PROTEIN DEGRADATION; PROTEIN FUNCTION; PROTEIN MODIFICATION; PROTEIN PROTEIN INTERACTION; PROTEIN STABILITY; PROTEIN SYNTHESIS INHIBITION; UPREGULATION; ANIMAL; BIOLOGICAL MODEL; C57BL MOUSE; CANCER STEM CELL; CHROMOSOME 21; CHROMOSOME 8; DRUG ANTAGONISM; ENZYMOLOGY; GENE TRANSLOCATION; GENETICS; HUMAN; INTRACELLULAR SPACE; METABOLISM; PATHOLOGY;

ANIMALS; CASPASE 3; CHROMOSOMES, HUMAN, PAIR 21; CHROMOSOMES, HUMAN, PAIR 8; CORE BINDING FACTOR ALPHA 2 SUBUNIT; DITERPENES, KAURANE; ENZYME ACTIVATION; HUMANS; INTRACELLULAR SPACE; LEUKEMIA, MYELOID, ACUTE; MICE; MICE, INBRED C57BL; MODELS, BIOLOGICAL; MOLECULAR TARGETED THERAPY; NEOPLASTIC STEM CELLS; ONCOGENE PROTEINS, FUSION; PROTEIN STABILITY; REACTIVE OXYGEN SPECIES; TRANSLOCATION, GENETIC; TUMOR SUPPRESSOR PROTEINS;

EID: 84859148351     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.3003562     Document Type: Article

References (32)

1. K. E. Elagib, A. N. Goldfarb, Oncogenic pathways of AML1-ETO in acute myeloid leukemia: Multifaceted manipulation of marrow maturation. Cancer Lett. 251, 179-186 (2007).
2. M. Higuchi, D. O'Brien, P. Kumaravelu, N. Lenny, E. J. Yeoh, J. R. Downing, Expression of a conditional AML1-ETO oncogene bypasses embryonic lethality and establishes a murine model of human t(8;21) acute myeloid leukemia. Cancer Cell 1, 63-74 (2002).
3. T. Okuda, Z. Cai, S. Yang, N. Lenny, C. Lyu, J. van Deursen, H. Harada, J. Downing, Expression of a knocked-in AML1-ETO leukemia gene inhibits the establishment of normal definitive hematopoiesis and directly generates dysplastic hematopoietic progenitors. Blood 91, 3134-3143 (1998).
4. T. S. Fenske, G. Pengue, V. Mathews, P. T. Hanson, S. E. Hamm, N. Riaz, T. A. Graubert, Stem cell expression of the AML1/ETO fusion protein induces a myeloproliferative disorder in mice. Proc. Natl. Acad. Sci. U.S.A. 101, 15184-15189 (2004).
5. Y. Yuan, L. Zhou, T. Miyamoto, H. Iwasaki, N. Harakawa, C. J. Hetherington, S. A. Burel, E. Lagasse, I. L. Weissman, K. Akashi, D. E. Zhang, AML1-ETO expression is directly involved in the development of acute myeloid leukemia in the presence of additional mutations. Proc. Natl. Acad. Sci. U.S.A. 98, 10398-10403 (2001).
6. Y. Y. Wang, L. J. Zhao, C. F. Wu, P. Liu, L. Shi, Y. Liang, S. M. Xiong, J. Q. Mi, Z. Chen, R. Ren, S. J. Chen, C-KIT mutation cooperates with full-length AML1-ETO to induce acute myeloid leukemia in mice. Proc. Natl. Acad. Sci. U.S.A. 108, 2450-2455 (2011).
7. M. Yan, E. Kanbe, L. F. Peterson, A. Boyapati, Y. Miao, Y. Wang, I. M. Chen, Z. Chen, J. D. Rowley, C. L. Willman, D. E. Zhang, A previously unidentified alternatively spliced isoform of t(8;21) transcript promotes leukemogenesis. Nat. Med. 12, 945-949 (2006).
8. G. B. Zhou, H. Kang, L. Wang, L. Gao, P. Liu, J. Xie, F. X. Zhang, X. Q. Weng, Z. X. Shen, J. Chen, L. J. Gu, M. Yan, D. E. Zhang, S. J. Chen, Z. Y. Wang, Z. Chen, Oridonin, a diterpenoid extracted from medicinal herbs, targets AML1-ETO fusion protein and shows potent antitumor activity with low adverse effects on t(8;21) leukemia in vitro and in vivo. Blood 109, 3441-3450 (2007).
9. S. Liu, R. B. Klisovic, T. Vukosavljevic, J. Yu, P. Paschka, L. Huynh, J. Pang, P. Neviani, Z. Liu, W. Blum, K. K. Chan, D. Perrotti, G. Marcucci, Targeting AML1/ETO-histone deacetylase repressor complex: A novel mechanism for valproic acid-mediated gene expression and cellular differentiation in AML1/ETO-positive acute myeloid leukemia cells. J. Pharmacol. Exp. Ther. 321, 953-960 (2007).
10. D. Grimwade, H. Walker, F. Oliver, K. Wheatley, C. Harrison, G. Harrison, J. Rees, I. Hann, R. Stevens, A. Burnett, A. Goldstone, The importance of diagnostic cytogenetics on outcome in AML: Analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children's Leukaemia Working Parties. Blood 92, 2322-2333 (1998).
11. R. Billström, B. Johansson, T. Fioretos, S. Garwicz, C. Malm, O. Zettervall, F. Mitelman, Poor survival in t(8;21) (q22;q22)-associated acute myeloid leukaemia with leukocytosis. Eur. J. Haematol. 59, 47-52 (1997).
12. J. M. Rowe, M. S. Tallman, How I treat acute myeloid leukemia. Blood 116, 3147-3156 (2010).
13. J. Jin, D. Z. Jiang, W. Y. Mai, H. T. Meng, W. B. Qian, H. Y. Tong, J. Huang, L. P. Mao, Y. Tong, L. Wang, Z. M. Chen, W. L. Xu, Homoharringtonine in combination with cytarabine and aclarubicin resulted in high complete remission rate after the first induction therapy in patients with de novo acute myeloid leukemia. Leukemia 20, 1361-1367 (2006).
14. Y. Y. Wang, G. B. Zhou, T. Yin, B. Chen, J. Y. Shi, W. X. Liang, X. L. Jin, J. H. You, G. Yang, Z. X. Shen, J. Chen, S. M. Xiong, G. Q. Chen, F. Xu, Y. W. Liu, Z. Chen, S. J. Chen, AML1-ETO and C-KIT mutation/overexpression in t(8;21) leukemia: Implication in stepwise leukemogenesis and response to Gleevec. Proc. Natl. Acad. Sci. U.S.A. 102, 1104-1109 (2005).
15. C. C. Chen, J. P. Gau, Y. B. Yu, C. H. Lu, K. D. Lee, J. Y. You, Prognosis and treatment outcome in patients with acute myeloid leukemia with t(8;21)(q22;q22). Adv. Ther. 24, 907-920 (2007).
16. B. Jiao, C. F. Wu, Y. Liang, H. M. Chen, S. M. Xiong, B. Chen, J. Y. Shi, Y. Y. Wang, J. H. Wang, Y. Chen, J. M. Li, L. J. Gu, J. Y. Tang, Z. X. Shen, B. W. Gu, W. L. Zhao, Z. Chen, S. J. Chen, AML1-ETO9a is correlated with C-KIT overexpression/mutations and indicates poor disease outcome in t(8;21) acute myeloid leukemia-M2. Leukemia 23, 1598-1604 (2009).
17. M. L. Circu, T. Y. Aw, Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic. Biol. Med. 48, 749-762 (2010).
18. J. E. Biaglow, R. A. Miller, The thioredoxin reductase/thioredoxin system: Novel redox targets for cancer therapy. Cancer Biol. Ther. 4, 6-13 (2005).
19. K. F. Tonissen, G. Di Trapani, Thioredoxin system inhibitors as mediators of apoptosis for cancer therapy. Mol. Nutr. Food Res. 53, 87-103 (2009).
20. Y. Lu, Z. Peng, T. Yuan, Q. Yin, L. Xia, G. Chen, Multi-sites cleavage of leukemogenic AML1-ETO fusion protein by caspase-3 and its contribution to increased apoptotic sensitivity. Leukemia 22, 378-386 (2008).
21. C. Kwok, B. B. Zeisig, J. Qiu, S. Dong, C. W. So, Transforming activity of AML1-ETO is independent of CBFb and ETO interaction but requires formation of homo-oligomeric complexes. Proc. Natl. Acad. Sci. U.S.A. 106, 2853-2858 (2009).
22. Y. Liu, M. D. Cheney, J. J. Gaudet, M. Chruszcz, S. M. Lukasik, D. Sugiyama, J. Lary, J. Cole, Z. Dauter, W. Minor, N. A. Speck, J. H. Bushweller, The tetramer structure of the Nervy homology two domain, NHR2, is critical for AML1/ETO's activity. Cancer Cell 9, 249-260 (2006).
23. G. J. Spangrude, S. Heimfeld, I. L. Weissman, Purification and characterization of mouse hematopoietic stem cells. Science 241, 58-62 (1988).
24. C. L. Li, G. R. Johnson, Murine hematopoietic stem and progenitor cells: I. Enrichment and biologic characterization. Blood 85, 1472-1479 (1995).
25. Y. Cheng, F. Qiu, T. Ikejima, Molecular mechanisms of oridonin-induced apoptosis and autophagy in murine fibrosarcoma L929 cells. Autophagy 5, 430-431 (2009).
26. F. Huang, C. Nie, Y. Yang, W. Yue, Y. Ren, Y. Shang, X. Wang, H. Jin, C. Xu, Q. Chen, Selenite induces redox-dependent Bax activation and apoptosis in colorectal cancer cells. Free Radic. Biol. Med. 46, 1186-1196 (2009).
27. C. H. Leung, S. P. Grill, W. Lam, Q. B. Han, H. D. Sun, Y. C. Cheng, Novel mechanism of inhibition of nuclear factor-kB DNA-binding activity by diterpenoids isolated from Isodon rubescens. Mol. Pharmacol. 68, 286-297 (2005).
28. F. H. Gao, X. H. Hu, W. Li, H. Liu, Y. J. Zhang, Z. Y. Guo, M. H. Xu, S. T. Wang, B. Jiang, F. Liu, Y. Z. Zhao, Y. Fang, F. Y. Chen, Y. L. Wu, Oridonin induces apoptosis and senescence in colorectal cancer cells by increasing histone hyperacetylation and regulation of p16, p21, p27 and c-myc. BMC Cancer 10, 610 (2010).
29. C. Wichmann, L. Chen, M. Heinrich, D. Baus, E. Pfitzner, M. Zornig, O. G. Ottmann, M. Grez, Targeting the oligomerization domain of ETO interferes with RUNX1/ETO oncogenic activity in t(8;21)-positive leukemic cells. Cancer Res. 67, 2280-2289 (2007).
30. Z. Y. Wang, Z. Chen, Acute promyelocytic leukemia: From highly fatal to highly curable. Blood 111, 2505-2515 (2008).
31. L. Wang, W. L. Zhao, J. S. Yan, P. Liu, H. P. Sun, G. B. Zhou, Z. Y. Weng, W. L. Wu, X. Q. Weng, X. J. Sun, Z. Chen, H. D. Sun, S. J. Chen, Eriocalyxin B induces apoptosis of t(8;21) leukemia cells through NF-kB and MAPK signaling pathways and triggers degradation of AML1-ETO oncoprotein in a caspase-3-dependent manner. Cell Death Differ. 14, 306-317 (2007).
32. M. Luthman, A. Holmgren, Rat liver thioredoxin and thioredoxin reductase: Purification and characterization. Biochemistry 21, 6628-6633 (1982).