Targeting EZH2-mediated methylation of histone 3 inhibits proliferation of pediatric acute monocytic leukemia cells in vitro

References

• Madhusoodhan PP, Carroll WL, Bhatla T. Progress and prospects in pediatric leukemia. Curr Probl Pediatr Adolesc Health Care. 2016;46(7):229–241. doi:10.1016/j.cppeds.2016.04.003.
   PubMed Web of Science ®Google Scholar
• Lonetti A, Pession A, Masetti R. Targeted therapies for pediatric AML: gaps and Perspective. Front Pediatr. 2019;7:463. doi:10.3389/fped.2019.00463.
   PubMed Web of Science ®Google Scholar
• Van Eys J, Pullen J, Head D, Boyett J, Crist W, Falletta J, Humphrey GB, Jackson J, Riccardi V, Brock B, et al. The French-American-British (FAB) classification of leukemia. The pediatric oncology group experience with lymphocytic leukemia. Cancer. 1986;57(5):1046–1051. doi:10.1002/1097-0142(19860301)57:5<1046::AID-CNCR2820570529>3.0.CO;2-0.
   PubMed Web of Science ®Google Scholar
• Tallman MS, Kim HT, Paietta E, Bennett JM, Dewald G, Cassileth PA, Wiernik PH, Rowe JM. Acute monocytic leukemia (French-American-British classification M5) does not have a worse prognosis than other subtypes of acute myeloid leukemia: a report from the Eastern cooperative oncology group. J Clin Oncol. 2004;22(7):1276–1286. doi:10.1200/JCO.2004.08.060.
   PubMed Web of Science ®Google Scholar
• Liu LP, et al. Prognostic Stratification of Molecularly and Clinically Distinct Subgroup in Children with Acute Monocytic Leukemia. 2020;9(11):3647–3655.
   Google Scholar
• Tsuchiya S, Yamabe M, Yamaguchi Y, Kobayashi Y, Konno T, Tada K. Establishment and characterization of a human acute monocytic leukemia cell line (THP-1). Int J Cancer. 1980;26(2):171–176. doi:10.1002/ijc.2910260208.
   PubMed Web of Science ®Google Scholar
• Odero MD, Zeleznik-Le NJ, Chinwalla V, Rowley JD. Cytogenetic and molecular analysis of the acute monocytic leukemia cell line THP-1 with an MLL-AF9 translocation. Genes Chromosomes Cancer. 2000;29(4):333–338. doi:10.1002/1098-2264(2000)9999:9999<::AID-GCC1040>3.0.CO;2-Z.
   PubMed Web of Science ®Google Scholar
• Hu ZD, Wei TT, Tang QQ, Ma N, Wang LL, Qin BD, Yin JR, Zhou L, Zhong RQ. Gene expression profile of THP-1 cells treated with heat-killed Candida albicans. Ann Transl Med. 2016;4(9):170. doi:10.21037/atm.2016.05.03.
   PubMed Web of Science ®Google Scholar
• Chanput W, Mes JJ, Wichers HJ. THP-1 cell line: an in vitro cell model for immune modulation approach. Int Immunopharmacol. 2014;23(1):37–45. doi:10.1016/j.intimp.2014.08.002.
   PubMed Web of Science ®Google Scholar
• Suzuki S, Nakano H, Takahashi S. Epigenetic regulation of the metallothionein-1A promoter by PU.1 during differentiation of THP-1 cells. Biochem Biophys Res Commun. 2013;433(3):349–353. doi:10.1016/j.bbrc.2013.03.007.
   PubMed Web of Science ®Google Scholar
• Davis FM, Gallagher KA. Epigenetic mechanisms in monocytes/macrophages regulate inflammation in cardiometabolic and vascular disease. Arterioscler Thromb Vasc Biol. 2019;39(4):623–634. doi:10.1161/ATVBAHA.118.312135.
   PubMed Web of Science ®Google Scholar
• Hoeksema MA, De Winther MP. Epigenetic regulation of monocyte and macrophage function. Antioxid Redox Signal0. 2016;25(14):758–774. doi:10.1089/ars.2016.6695.
   PubMed Web of Science ®Google Scholar
• Ciavatta DJ, et al. Epigenetic basis for aberrant upregulation of autoantigen genes in humans with ANCA vasculitis. J Clin Invest. 2010;120(9):3209–3219. doi:10.1172/JCI40034.
   PubMed Web of Science ®Google Scholar
• Gan L, Yang Y, Li Q, Feng Y, Liu T, Guo W. Epigenetic Regulation of Cancer Progression by EZH2: From Biological Insights to Therapeutic Potential. 2018;6:10.
   Google Scholar
• Wang W, Qin JJ, Voruganti S, Nag S, Zhou J, Zhang R. Polycomb group (pcg) proteins and human cancers: multifaceted functions and therapeutic implications. Med Res Rev. 2015;35(6):1220–1267.
   PubMed Web of Science ®Google Scholar
• Chan HL, Morey L. Emerging roles for polycomb-group proteins in stem cells and cancer. Trends Biochem Sci. 2019;44(8):688–700. doi:10.1016/j.tibs.2019.04.005.
   PubMed Web of Science ®Google Scholar
• Pasini D, Di Croce L. Emerging roles for Polycomb proteins in cancer. Curr Opin Genet Dev. 2016;36:50–58. doi:10.1016/j.gde.2016.03.013.
   PubMed Web of Science ®Google Scholar
• Varambally S, Dhanasekaran SM, Zhou M, Barrette TR, Kumar-Sinha C, Sanda MG, Ghosh D, Pienta KJ, Sewalt RGAB, Otte AP, et al. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature. 2002;419(6907):624–629. doi:10.1038/nature01075.
   PubMed Web of Science ®Google Scholar
• Raaphorst FM, Meijer CJLM, Fieret E, Blokzijl T, Mommers E, Buerger H, Packeisen J, Sewalt RAB, Ottet AP, Van Diest PJ, et al. Poorly differentiated breast carcinoma is associated with increased expression of the human polycomb group EZH2 gene. Neoplasia. 2003;5(6):481–488. doi:10.1016/S1476-5586(03)80032-5.
   PubMed Web of Science ®Google Scholar
• Croonquist PA, Van Ness B. The polycomb group protein enhancer of zeste homolog 2 (EZH 2) is an oncogene that influences myeloma cell growth and the mutant ras phenotype. Oncogene. 2005;24(41):6269–6280. doi:10.1038/sj.onc.1208771.
   PubMed Web of Science ®Google Scholar
• Zhang P, Xiao Z, Wang S, Zhang M, Wei Y, Hang Q, Kim J, Yao F, Rodriguez-Aguayo C, Ton BN, et al. ZRANB1 is an ezh2 deubiquitinase and a potential therapeutic target in breast cancer. Cell Rep. 2018;23(3):823–837. doi:10.1016/j.celrep.2018.03.078.
   PubMed Web of Science ®Google Scholar
• Wang J, Cheng P, Pavlyukov MS, Yu H, Zhang Z, Kim S-H, Minata M, Mohyeldin A, Xie W, Chen D, et al. Targeting NEK2 attenuates glioblastoma growth and radioresistance by destabilizing histone methyltransferase EZH2. J Clin Invest. 2017;127(8):3075–3089. doi:10.1172/JCI89092.
   PubMed Web of Science ®Google Scholar
• Yang PM, Hong YH, Hsu KC, Liu TP. p38α/S1P/SREBP2 activation by the SAM-competitive EZH2 inhibitor GSK343 limits its anticancer activity but creates a druggable vulnerability in hepatocellular carcinoma. Am J Cancer Res. 2019;9(10):2120–2139.
   PubMed Web of Science ®Google Scholar
• Huang K, Sun R, Chen J, Yang Q, Wang Y, Zhang Y, Xie K, Zhang T, Li R, Zhao Q, et al. A novel EZH2 inhibitor induces synthetic lethality and apoptosis in PBRM1-deficient cancer cells. Cell Cycle. 2020;19(7):758–771. doi:10.1080/15384101.2020.1729450.
   PubMed Web of Science ®Google Scholar
• Yomtoubian S, Lee SB, Verma A, Izzo F, Markowitz G, Choi H, Cerchietti L, Vahdat L, Brown KA, Andreopoulou E, et al. Inhibition of EZH2 catalytic activity selectively targets a metastatic subpopulation in triple-negative breast cancer. Cell Rep. 2020;30(3):755–770.e6. doi:10.1016/j.celrep.2019.12.056.
   PubMed Web of Science ®Google Scholar
• Jin X, Yang C, Fan P, Xiao J, Zhang W, Zhan S, Liu T, Wang D, Wu H. CDK5/FBW7-dependent ubiquitination and degradation of EZH2 inhibits pancreatic cancer cell migration and invasion. J Biol Chem. 2017;292(15):6269–6280. doi:10.1074/jbc.M116.764407.
   PubMed Web of Science ®Google Scholar
• Wang Q, Chen X, Jiang Y, Liu S, Liu H, Sun X, Zhang H, Liu Z, Tao Y, Li C, et al. Elevating H3K27me3 level sensitizes colorectal cancer to oxaliplatin. J Mol Cell Biol. 2020;12(2):125–137. doi:10.1093/jmcb/mjz032.
   PubMed Web of Science ®Google Scholar
• Ciarapica R, Miele L, Giordano A, Locatelli F, Rota R. Enhancer of zeste homolog 2 (EZH2) in pediatric soft tissue sarcomas: first implications. BMC Med. 2011;9(1):63. doi:10.1186/1741-7015-9-63.
   PubMedGoogle Scholar
• Venneti S, Garimella MT, Sullivan LM, Martinez D, Huse JT, Heguy A, Santi M, Thompson CB, Judkins AR. Evaluation of histone 3 lysine 27 trimethylation (H3K27me3) and enhancer of zest 2 (EZH2) in pediatric glial and glioneuronal tumors shows decreased H3K27me3 in H3F3A K27M mutant glioblastomas. Brain Pathol. 2013;23(5):558–564. doi:10.1111/bpa.12042.
   PubMed Web of Science ®Google Scholar
• Basheer F, Giotopoulos G. Contrasting Requirements during Disease Evolution Identify EZH2 as a Therapeutic Target in AML. J Exp Med. 2019;2164:966–981.
   Google Scholar
• Mechaal A, Menif S, Abbes S, Safra I. EZH2, new diagnosis and prognosis marker in acute myeloid leukemia patients. Adv Med Sci. 2019;64(2):395–401. doi:10.1016/j.advms.2019.07.002.
   PubMed Web of Science ®Google Scholar
• Al-Ghabkari A, Narendran A. In vitro characterization of a potent p53-MDM2 inhibitor, RG7112 in neuroblastoma cancer cell lines. Cancer Biother Radiopharm. 2019;34(4):252–257. doi:10.1089/cbr.2018.2732.
   PubMed Web of Science ®Google Scholar
• Al-Ghabkari A, Deng JT, McDonald PC, Dedhar S, Alshehri M, Walsh MP, MacDonald JA. A novel inhibitory effect of oxazol-5-one compounds on ROCKII signaling in human coronary artery vascular smooth muscle cells. Sci Rep. 2016;6(1):32118. doi:10.1038/srep32118.
   PubMedGoogle Scholar
• Huet S, Xerri L, Tesson B, Mareschal S, Taix S, Mescam-Mancini L, Sohier E, Carrère M, Lazarovici J, Casasnovas O, et al. EZH2 alterations in follicular lymphoma: biological and clinical correlations. Blood Cancer J. 2017;7(4):e555. doi:10.1038/bcj.2017.32.
   PubMedGoogle Scholar
• Akpa CA, Kleo K, Lenze D, Oker E, Dimitrova L, Hummel M, Bertolini F. DZNep-mediated apoptosis in B-cell lymphoma is independent of the lymphoma type, EZH2 mutation status and MYC, BCL2 or BCL6 translocations. PLoS One. 2019;14(8):e0220681. doi:10.1371/journal.pone.0220681.
   PubMed Web of Science ®Google Scholar
• Yu T, Wang Y, Hu Q, Wu W, Wu Y, Wei W, Han D, You Y, Lin N, Liu N, et al. The EZH2 inhibitor GSK343 suppresses cancer stem-like phenotypes and reverses mesenchymal transition in glioma cells. Oncotarget. 2017;8(58):98348–98359. doi:10.18632/oncotarget.21311.
   PubMedGoogle Scholar
• Girard N, Bazille C, Lhuissier E, Benateau H, Llombart-Bosch A, Boumediene K, Bauge C, Alonso MM. 3-deazaneplanocin A (DZNep), an inhibitor of the histone methyltransferase EZH2, induces apoptosis and reduces cell migration in chondrosarcoma cells. PLoS One. 2014;9(5):e98176. doi:10.1371/journal.pone.0098176.
   PubMed Web of Science ®Google Scholar
• Huang S, Wang Z, Zhou J, Huang J, Zhou L, Luo J, Wan YY, Long H, Zhu B. EZH2 inhibitor GSK126 suppresses anti-tumor immunity by driving production of myeloid-derived suppressor cells. Cancer Res. 2019;79(8):2009–2020.
   Web of Science ®Google Scholar
• Qi W, Chan H, Teng L, Li L, Chuai S, Zhang R, Zeng J, Li M, Fan H, Lin Y, et al. Selective inhibition of Ezh2 by a small molecule inhibitor blocks tumor cells proliferation. Proc Natl Acad Sci U S A. 2012;109(52):21360–21365. doi:10.1073/pnas.1210371110.
   PubMed Web of Science ®Google Scholar
• Lindsay CD, Kostiuk MA, Harris J, O’Connell DA, Seikaly H, Biron VL. Efficacy of EZH2 Inhibitory Drugs in Human Papillomavirus-positive and Human Papillomavirus-negative Oropharyngeal Squamous Cell Carcinomas. 2017;9:95.
   Google Scholar
• Konze KD, Ma A, Li F, Barsyte-Lovejoy D, Parton T, MacNevin CJ, Liu F, Gao C, Huang X-P, Kuznetsova E, et al. An orally bioavailable chemical probe of the lysine methyltransferases EZH2 and EZH1. ACS Chem Biol. 2013;8(6):1324–1334. doi:10.1021/cb400133j.
   PubMed Web of Science ®Google Scholar
• Knutson SK, Kawano S, Minoshima Y, Warholic NM, Huang K-C, Xiao Y, Kadowaki T, Uesugi M, Kuznetsov G, Kumar N, et al. Selective inhibition of EZH2 by EPZ-6438 leads to potent antitumor activity in EZH2-mutant non-hodgkin lymphoma. Mol Cancer Ther. 2014;13(4):842–854. doi:10.1158/1535-7163.MCT-13-0773.
   PubMed Web of Science ®Google Scholar
• Zingg D, Debbache J, Schaefer SM, Tuncer E, Frommel SC, Cheng P, Arenas-Ramirez N, Haeusel J, Zhang Y, Bonalli M, et al. The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumour suppressors. Nat Commun. 2015;6(1):6051. doi:10.1038/ncomms7051.
   PubMedGoogle Scholar
• Greer EL, Shi Y. Histone methylation: a dynamic mark in health, disease and inheritance. Nat Rev Genet. 2012;13(5):343–357. doi:10.1038/nrg3173.
   PubMed Web of Science ®Google Scholar
• Zeng D, Liu M, Pan J. Blocking EZH2 methylation transferase activity by GSK126 decreases stem cell-like myeloma cells. Oncotarget. 2017;8(2):3396–3411. doi:10.18632/oncotarget.13773.
   PubMedGoogle Scholar
• Adhikary G, Grun D, Balasubramanian S, Kerr C, Huang JM, Eckert RL. Survival of skin cancer stem cells requires the Ezh2 polycomb group protein. Carcinogenesis. 2015;36(7):800–810. doi:10.1093/carcin/bgv064.
   PubMed Web of Science ®Google Scholar
• Grinshtein N, Rioseco CC, Marcellus R, Uehling D, Aman A, Lun X, Muto O, Podmore L, Lever J, Shen Y, et al. Small molecule epigenetic screen identifies novel EZH2 and HDAC inhibitors that target glioblastoma brain tumor-initiating cells. Oncotarget. 2016;7(37):59360–59376. doi:10.18632/oncotarget.10661.
   PubMedGoogle Scholar
• Dhillon AS, Hagan S, Rath O, Kolch W. MAP kinase signalling pathways in cancer. Oncogene. 2007;26(22):3279–3290. doi:10.1038/sj.onc.1210421.
   PubMed Web of Science ®Google Scholar
• Porta C, Paglino C, Mosca A. Targeting PI3K/Akt/mTOR signaling in cancer. Front Oncol. 2014;4:64. doi:10.3389/fonc.2014.00064.
   PubMedGoogle Scholar
• Sugimoto K, Toyoshima H, Sakai R, Miyagawa K, Hagiwara K, Ishikawa F, Takaku F, Yazaki Y, Hirai H. Frequent mutations in the p53 gene in human myeloid leukemia cell lines. Blood. 1992;79(9):2378–2383. doi:10.1182/blood.V79.9.2378.2378.
   PubMed Web of Science ®Google Scholar
• Yardley DA. Drug resistance and the role of combination chemotherapy in improving patient outcomes. Int J Breast Cancer. 2013;2013:137414. doi:10.1155/2013/137414.
   PubMedGoogle Scholar
• Al-Ghabkari A, Perinpanayagam MA, Narendran A. Inhibition of PI3K/mTOR pathways with GDC-0980 in pediatric leukemia: impact on abnormal FLT-3 activity and cooperation with intracellular signaling targets. Curr Cancer Drug Targets. 2019;19(10):828–837. doi:10.2174/1568009619666190326120833.
   PubMed Web of Science ®Google Scholar
• Walker CJ, Oaks JJ, Santhanam R, Neviani P, Harb JG, Ferenchak G, Ellis JJ, Landesman Y, Eisfeld A-K, Gabrail NY, et al. Preclinical and clinical efficacy of XPO1/CRM1 inhibition by the karyopherin inhibitor KPT-330 in Ph+ leukemias. Blood. 2013;122(17):3034–3044. doi:10.1182/blood-2013-04-495374.
   PubMed Web of Science ®Google Scholar
• Kuruvilla J, Savona M, Baz R, Mau-Sorensen PM, Gabrail N, Garzon R, Stone R, Wang M, Savoie L, Martin P, et al. Selective inhibition of nuclear export with selinexor in patients with non-Hodgkin lymphoma. Blood. 2017;129(24):3175–3183. doi:10.1182/blood-2016-11-750174.
   PubMed Web of Science ®Google Scholar
• Gounder MM, et al. Phase IB study of selinexor, a first-in-class inhibitor of nuclear export, in patients with advanced refractory bone or soft tissue sarcoma. J Clin Oncol. 2016;34(26):3166–3174. doi:10.1200/JCO.2016.67.6346.
   PubMed Web of Science ®Google Scholar
• Bahlis NJ, Sutherland H, White D, Sebag M, Lentzsch S, Kotb R, Venner CP, Gasparetto C, Del Col A, Neri P, et al. Selinexor plus low-dose bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma. Blood. 2018;132(24):2546–2554. doi:10.1182/blood-2018-06-858852.
   PubMed Web of Science ®Google Scholar
• Wang AY, et al. A phase I study of selinexor in combination with high-dose cytarabine and mitoxantrone for remission induction in patients with acute myeloid leukemia. J Hematol Oncol. 2018;11(1):4. doi:10.1186/s13045-017-0550-8.
   PubMed Web of Science ®Google Scholar
• Kim KH, Roberts CW. Targeting EZH2 in cancer. Nat Med. 2016;22(2):128–134. doi:10.1038/nm.4036.
   PubMed Web of Science ®Google Scholar
• McCabe MT, et al. Mutation of A677 in histone methyltransferase EZH2 in human B-cell lymphoma promotes hypertrimethylation of histone H3 on lysine 27 (H3K27). Proc Natl Acad Sci U S A. 2012;109(8):2989–2994. doi:10.1073/pnas.1116418109.
   PubMed Web of Science ®Google Scholar
• Christofides A, Karantanos T, Bardhan K, Boussiotis VA. Epigenetic regulation of cancer biology and anti-tumor immunity by EZH2. Oncotarget. 2016;7(51):85624–85640.
   PubMedGoogle Scholar
• Tabbal H, Septier A, Mathieu M, Drelon C, Rodriguez S, Djari C, Batisse-Lignier M, Tauveron I, Pointud J-C, Sahut-Barnola I, et al. EZH2 cooperates with E2F1 to stimulate expression of genes involved in adrenocortical carcinoma aggressiveness. Br J Cancer. 2019;121(5):384–394. doi:10.1038/s41416-019-0538-y.
   PubMed Web of Science ®Google Scholar
• Papale M, Ferretti E, Battaglia G, Bellavia D, Mai A, Tafani M. EZH2, HIF-1, and their inhibitors: an overview on pediatric cancers. Front Pediatr. 2018;6:328. doi:10.3389/fped.2018.00328.
   PubMed Web of Science ®Google Scholar
• Song X, Zhang L, Gao T, Ye T, Zhu Y, Lei Q, Feng Q, He B, Deng H, Yu L, et al. Selective inhibition of EZH2 by ZLD10A blocks H3K27 methylation and kills mutant lymphoma cells proliferation. Biomed Pharmacother. 2016;81:288–294. doi:10.1016/j.biopha.2016.04.019.
   PubMed Web of Science ®Google Scholar
• Villanueva MT. Anticancer drugs: all roads lead to EZH2 inhibition. Nat Rev Drug Discov. 2017;16(4):239.
   PubMed Web of Science ®Google Scholar
• Bradley WD, Arora S, Busby J, Balasubramanian S, Gehling V, Nasveschuk C, Vaswani R, Yuan -C-C, Hatton C, Zhao F, et al. EZH2 inhibitor efficacy in non-Hodgkin’s lymphoma does not require suppression of H3K27 monomethylation. Chem Biol. 2014;21(11):1463–1475. doi:10.1016/j.chembiol.2014.09.017.
   PubMedGoogle Scholar
• Ozes AR, Pulliam N, Ertosun MG, Yilmaz O, Tang J, Copuroglu E, Matei D, Ozes ON, Nephew KP. Protein kinase A-mediated phosphorylation regulates STAT3 activation and oncogenic EZH2 activity. Oncogene. 2018;37(26):3589–3600. doi:10.1038/s41388-018-0218-z.
   PubMed Web of Science ®Google Scholar
• Chen S, Bohrer LR, Rai AN, Pan Y, Gan L, Zhou X, Bagchi A, Simon JA, Huang H. Cyclin-dependent kinases regulate epigenetic gene silencing through phosphorylation of EZH2. Nat Cell Biol. 2010;12(11):1108–1114. doi:10.1038/ncb2116.
   PubMed Web of Science ®Google Scholar
• Bott SR, Arya M, Kirby RS, Williamson M. p21WAF1/CIP1 gene is inactivated in metastatic prostatic cancer cell lines by promoter methylation. Prostate Cancer Prostatic Dis. 2005;8(4):321–326. doi:10.1038/sj.pcan.4500822.
   PubMed Web of Science ®Google Scholar
• Askari M, Sobti RC, Nikbakht M, Sharma SC. Aberrant promoter hypermethylation of p21 (WAF1/CIP1) gene and its impact on expression and role of polymorphism in the risk of breast cancer. Mol Cell Biochem. 2013;382(1–2):19–26. doi:10.1007/s11010-013-1696-5.
   PubMed Web of Science ®Google Scholar
• Zhu J, Dou Z, Sammons MA, Levine AJ, Berger SL. Lysine methylation represses p53 activity in teratocarcinoma cancer cells. Proc Natl Acad Sci U S A. 2016;113(35):9822–9827. doi:10.1073/pnas.1610387113.
   PubMed Web of Science ®Google Scholar
• Ito T, Nishida N, Fukuda Y, Nishimura T, Komeda T, Nakao K. Alteration of the p14(ARF) gene and p53 status in human hepatocellular carcinomas. J Gastroenterol. 2004;39(4):355–361. doi:10.1007/s00535-003-1302-9.
   PubMed Web of Science ®Google Scholar
• Yi L, Sun Y, Levine A. Selected drugs that inhibit DNA methylation can preferentially kill p53 deficient cells. Oncotarget. 2014;5(19):8924–8936. doi:10.18632/oncotarget.2441.
   PubMedGoogle Scholar
• Fan T, Jiang S, Chung N, Alikhan A, Ni C, Lee CC, Hornyak TJ. EZH2-dependent suppression of a cellular senescence phenotype in melanoma cells by inhibition of p21/CDKN1A expression. Mol Cancer Res. 2011;9(4):418–429. doi:10.1158/1541-7786.MCR-10-0511.
   PubMed Web of Science ®Google Scholar
• Talati C, Sweet KL. Nuclear transport inhibition in acute myeloid leukemia: recent advances and future perspectives. Int J Hematol Oncol. 2018;7(3):Ijh04. doi:10.2217/ijh-2018-0001.
   PubMedGoogle Scholar