The major oncogenic driver of acute promyelocytic leukemia (APL) is the

The major oncogenic driver of acute promyelocytic leukemia (APL) is the fusion protein PML-RAR originated from the chromosomal translocation t(15;17). target both ATRA- sensitive and resistant APL cells through their distinct acting mechanism, and are potential drug leads for APL treatment. <0.05 was considered significant. SUPPLEMENTARY MATERIALS FIGURES AND TABLES Click here to view.(3.0M, pdf) ACKNOWLEDGMENTS AND FUNDING We thank Dr. AEB071 Guo-qiang Chen, Dr. Ying-li Wu and Dr. Jun Zhu from Shanghai Jiao-Tong University School of Medicine for kindly providing NB4, NB4-LR1 and NB4-LR2 cells, and PSG5-PML-RAR expression plasmid. This work was supported by the grants from the National Nature Science Fund of China (NSFC-31471318, NSFC-31271453, NSFC-91129302 and NSFC-81301888), the National Institutes of Health (CA140980, GM089927). Footnotes CONFLICTS OF INTEREST The authors declare no competing financial interests. REFERENCES 1. Coombs CC, DeAngelis LM, Feusner JH, Rowe JM, Tallman MS. Pseudotumor Cerebri in Acute Promyelocytic Leukemia Patients on Intergroup Protocol 0129: Clinical Description and Recommendations for New Diagnostic Criteria. Clin Lymphoma Myeloma Leuk. 2016;16:146C151. [PMC free article] [PubMed] 2. Wang ZY, Chen Z. Acute promyelocytic leukemia: from highly fatal to highly curable. AEB071 Blood. 2008;111:2505C2515. [PubMed] 3. Tussie-Luna MI, Rozo L, Roy AL. Pro-proliferative function of the long isoform of PML-RARalpha involved in acute promyelocytic leukemia. Oncogene. 2006;25:3375C3386. [PubMed] 4. Ablain J, de The H. Retinoic acid signaling in cancer: The parable of acute promyelocytic leukemia. Int J Cancer. 2014;135:2262C2272. [PubMed] 5. Bernardi R, Pandolfi PP. Role of PML and the PML-nuclear body in the control of programmed cell death. Oncogene. 2003;22:9048C9057. [PubMed] 6. Bernardi R, Pandolfi PP. Structure, dynamics and functions of promyelocytic leukaemia nuclear bodies. Nat Rev Mol Cell Biol. 2007;8:1006C1016. [PubMed] 7. de The H, Chen Z. Acute promyelocytic leukaemia: novel insights into the mechanisms of cure. Nat Rev Cancer. 2010;10:775C783. [PubMed] 8. Nasr R, Lallemand-Breitenbach V, Zhu J, Guillemin MC, de The H. Therapy-induced PML/RARA proteolysis and acute promyelocytic leukemia cure. Clin Cancer Res. 2009;15:6321C6326. [PubMed] 9. Nervi C, Ferrara FF, Fanelli M, Rippo MR, Tomassini B, Ferrucci PF, Ruthardt M, Gelmetti V, Gambacorti-Passerini C, Diverio D, Grignani F, Pelicci PG, Testi R. Caspases mediate retinoic acid-induced degradation of the acute promyelocytic leukemia PML/RARalpha fusion protein. Blood. 1998;92:2244C2251. [PubMed] 10. Zhu J, Gianni M, Kopf E, Honore N, Chelbi-Alix M, Koken M, Quignon F, Rochette-Egly C, de The H. Retinoic acid induces proteasome-dependent degradation of retinoic acid receptor alpha (RARalpha) and oncogenic RARalpha fusion proteins. Proc Natl Acad Sci U S A. 1999;96:14807C14812. [PMC free article] [PubMed] 11. Hatake K, Uwai M, Ohtsuki T, Tomizuka H, Izumi T, Yoshida M, Miura Y. Rare but important adverse effects AEB071 of all-trans retinoic acid in acute promyelocytic leukemia and their management. Int J Hematol. 1997;66:13C19. [PubMed] 12. Su YC, Dunn P, Shih LY, Kuo MC, Chang H, Wu JH, Lin TL, Wang PN, Tang TC, Hung YS. Retinoic acid syndrome in patients following the treatment of acute promyelocytic leukemia with all-trans retinoic acid. Chang Gung medical journal. 2009;32:535C542. [PubMed] 13. Tomita A, Kiyoi H, Naoe T. Mechanisms of action and resistance to all-trans retinoic acid (ATRA) and arsenic trioxide (As2O 3) in acute promyelocytic leukemia. AEB071 Int J Hematol. 2013;97:717C725. [PubMed] 14. Gallagher RE. Retinoic acid resistance AEB071 in acute promyelocytic Rabbit Polyclonal to NSE leukemia. Leukemia. 2002;16:1940C1958. [PubMed] 15. Zhang XW, Yan XJ, Zhou ZR, Yang FF, Wu ZY, Sun HB, Liang WX, Song AX, Lallemand-Breitenbach V, Jeanne M, Zhang QY, Yang HY, Huang QH, Zhou GB, Tong JH, Zhang Y, et al. Arsenic trioxide controls the fate of the PML-RARalpha oncoprotein by directly binding PML. Science. 2010;328:240C243. [PubMed] 16. Lallemand-Breitenbach V, Jeanne M, Benhenda S, Nasr R, Lei M, Peres L, Zhou J, Zhu J, Raught B, de The H. Arsenic degrades PML or PML-RARalpha through.