393
Views
8
CrossRef citations to date
0
Altmetric
Review

Targeting epigenetic regulators in the treatment of T-cell lymphoma

&
Pages 127-139 | Received 28 Sep 2019, Accepted 02 Jan 2020, Published online: 22 Jan 2020

References

  • Armitage JO. The aggressive peripheral T-cell lymphomas: 2017. Am J Hematol. 2017;92(7):706–715.
  • Laribi K, Alani M, Truong C, et al. Evolving strategies for the treatment of T-cell lymphoma: A systematic review and recent patents. Recent Pat Anticancer Drug Discov. 2018;13(3):308–340.
  • Lue JK, Amengual JE, O’Connor OA. Epigenetics and lymphoma: Can we use epigenetics to prime or reset chemoresistant lymphoma programs? Curr Oncol Rep. 2015;17(9):40.
  • Abouyabis AN, Shenoy PJ, Lechowicz MJ, et al. Incidence and outcomes of the peripheral T-cell lymphoma subtypes in the United States. Leuk Lymphoma. 2008;49(11):2099–2107.
  • Swerdlow S, Campo E, Harris N, et al. eds. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon: International Agency for Research on Cancer; 2017.
  • Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375–2390.
  • Vose J, Armitage J, Weisenburger D. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol. 2008;26(25):4124–4130.
  • Jiang M, Bennani NN, Feldman AL. Lymphoma classification update: T-cell lymphomas, Hodgkin lymphomas, and histiocytic/dendritic cell neoplasms. Expert Rev Hematol. 2017;10(3):239–249.
  • Sandell RF, Boddicker RL, Feldman AL. Genetic landscape and classification of peripheral T cell lymphomas. Curr Oncol Rep. 2017;19(4):28.
  • Sermer D, Pasqualucci L, Wendel HG, et al. Emerging epigenetic-modulating therapies in lymphoma. Nat Rev Clin Oncol. 2019 Aug;16(8):494-507.
  • Sandoval J, Diaz-Lagares A, Salgado R, et al. MicroRNA expression profiling and DNA methylation signature for deregulated microRNA in cutaneous T-cell lymphoma. J Invest Dermatol. 2015;135(4):1128–1137.
  • Wouters BJ, Delwel R. Epigenetics and approaches to targeted epigenetic therapy in acute myeloid leukemia. Blood. 2016;127(1):42–52.
  • Pfister SX, Ashworth A. Marked for death: targeting epigenetic changes in cancer. Nat Rev Drug Discov. 2017;16(4):241–263.
  • Nosaka K, Maeda M, Tamiya S, et al. Increasing methylation of the CDKN2A gene is associated with the progression of adult T-cell leukemia. Cancer Res. 2000;60(4):1043–1048.
  • Hoareau-Aveilla C, Meggetto F. Crosstalk between microRNA and DNA methylation offers potential biomarkers and targeted therapies in ALK-positive lymphomas. Cancers (Basel). 2017 Aug 3;9(8). pii: E100.
  • Hyun K, Jeon J, Park K, et al. Writing, erasing and reading histone lysine methylations. Exp Mol Med. 2017;49(4):e324.
  • Jiang Y, Hatzi K, Shaknovich R. Mechanisms of epigenetic deregulation in lymphoid neoplasms. Blood. 2013;121(21):4271–4279.
  • Hofmann WK, Tsukasaki K, Takeuchi N, et al. Methylation analysis of cell cycle control genes in adult T-cell leukemia/lymphoma. Leuk Lymphoma. 2001;42(5):1107–1109.
  • Sato H, Oka T, Shinnou Y, et al. Multi-step aberrant cpg island hyper-methylation is associated with the progression of adult T–cell leukemia/lymphoma. Am J Pathol. 2010 Jan;176(1):402–415.
  • Watanabe M, Nakahata S, Hamasaki M, et al. Downregulation of CDKN1A in adult T-cell leukemia/lymphoma despite overexpression of CDKN1A in human T-lymphotropic virus 1-infected cell lines. J Virol. 2010;84(14):6966–6977.
  • Taniguchi A, Nemoto Y, Yokoyama A, et al. Promoter methylation of the bone morphogenetic protein-6 gene in association with adult T-cell leukemia. Int J Cancer. 2008;123(8):1824–1831.
  • Yang Y, Takeuchi S, Tsukasaki K, et al. Methylation analysis of the adenomatous polyposis coli (APC) gene in adult T-cell leukemia/lymphoma. Leuk Res. 2005;29(1):47–51.
  • Tsuji T, Sugahara K, Tsuruda K, et al. Clinical and oncologic implications in epigenetic down-regulation of CD26/dipeptidyl peptidase IV in adult T-cell leukemia cells. Int J Hematol. 2004;80(3):254–260.
  • Watanabe T. Adult T-cell leukemia: molecular basis for clonal expansion and transformation of HTLV-1-infected T cells. Blood. 2017;129(9):1071–1081.
  • Wu J, Wood GS. Reduction of Fas/CD95 promoter methylation, upregulation of Fas protein, and enhancement of sensitivity to apoptosis in cutaneous T-cell lymphoma. Arch Dermatol. 2011;147(4):443–449.
  • Wilcox RA. Cutaneous T-cell lymphoma: 2016 update on diagnosis, risk-stratification, and management. Am J Hematol. 2016;91(1):151–165.
  • Sibbesen NA, Kopp KL, Litvinov IV, et al. Jak3, STAT3, and STAT5 inhibit expression of miR-22, a novel tumor suppressor microRNA, in cutaneous T-Cell lymphoma. Oncotarget. 2015;6(24):20555–20569.
  • Koboldt DC, Chen K, Wylie T, et al. VarScan: variant detection in massively parallel sequencing of individual and pooled samples. Bioinformatics. 2009;25(17):2283–2285.
  • Vallois D, Dobay MP, Morin RD, et al. Activating mutations in genes related to TCR signaling in angioimmunoblastic and other follicular helper T-cell-derived lymphomas. Blood. 2016;128(11):1490–1502.
  • Schatz JH, Horwitz SM, Teruya-Feldstein J, et al. Targeted mutational profiling of peripheral T-cell lymphoma not otherwise specified highlights new mechanisms in a heterogeneous pathogenesis. Leukemia. 2015 Jan;29(1):237–241. England.
  • Zhu X, He F, Zeng H, et al. Identification of functional cooperative mutations of SETD2 in human acute leukemia. Nat Genet. 2014;46(3):287–293.
  • da Silva Almeida AC, Abate F, Khiabanian H, et al. The mutational landscape of cutaneous T cell lymphoma and Sezary syndrome. Nat Genet. 2015;47(12):1465–1470.
  • Lemonnier F, Gaulard P, de Leval L. New insights in the pathogenesis of T-cell lymphomas. Curr Opin Oncol. 2018;30(5):277–284.
  • Bergmann AK, Fataccioli V, Castellano G, et al. DNA methylation profiling of hepatosplenic T-cell lymphoma. Haematologica. 2019 Mar;104(3):e104–e107.
  • Lee S, Park HY, Kang SY, et al. Genetic alterations of JAK/STAT cascade and histone modification in extranodal NK/T-cell lymphoma nasal type. Oncotarget. 2015;6(19):17764–17776.
  • Cortes JR, Palomero T. The curious origins of angioimmunoblastic T-cell lymphoma. Curr Opin Hematol. 2016;23(4):434–443.
  • Couronne L, Bastard C, Bernard OA. TET2 and DNMT3A mutations in human T-cell lymphoma. N Engl J Med. 2012;366(1):95–96.
  • Palomero T, Couronne L, Khiabanian H, et al. Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas. Nat Genet. 2014;46(2):166–170.
  • Lemonnier F, Couronne L, Parrens M, et al. Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters. Blood. 2012;120(7):1466–1469.
  • Wang C, McKeithan TW, Gong Q, et al. IDH2R172 mutations define a unique subgroup of patients with angioimmunoblastic T-cell lymphoma. Blood. 2015;126(15):1741–1752.
  • Cairns RA, Iqbal J, Lemonnier F, et al. IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma. Blood. 2012;119(8):1901–1903.
  • Kotredes KP, Razmpour R, Lutton E, et al. Characterization of cancer-associated IDH2 mutations that differ in tumorigenicity, chemosensitivity and 2-hydroxyglutarate production. Oncotarget. 2019;10(28):2675–2692.
  • Ha JS, Jeon DS, Kim JR, et al. Analysis of the Ten-Eleven Translocation 2 (TET2) gene mutation in myeloproliferative neoplasms. Ann Clin Lab Sci. 2014;44(2):173–179.
  • Shenoy N, Bhagat T, Nieves E, et al. Upregulation of TET activity with ascorbic acid induces epigenetic modulation of lymphoma cells. Blood Cancer J. 2017;7(7):e587.
  • Zang S, Li J, Yang H, et al. Mutations in 5-methylcytosine oxidase TET2 and RhoA cooperatively disrupt T cell homeostasis. J Clin Invest. 2017;127(8):2998–3012.
  • Ji MM, Huang YH, Huang JY, et al. Histone modifier gene mutations in peripheral T-cell lymphoma not otherwise specified. Haematologica. 2018 Apr;103(4):679–687.
  • Fernandez-Pol S, Ma L, Joshi RP, et al. A survey of somatic mutations in 41 genes in a cohort of T-cell lymphomas identifies frequent mutations in genes involved in epigenetic modification. Appl Immunohistochem Mol Morphol. 2019 Jul;27(6):416-422.
  • Roberti A, Dobay MP, Bisig B, et al. Type II enteropathy-associated T-cell lymphoma features a unique genomic profile with highly recurrent SETD2 alterations. Nat Commun. 2016;7:12602.
  • Moffitt AB, Ondrejka SL, McKinney M, et al. Enteropathy-associated T cell lymphoma subtypes are characterized by loss of function of SETD2. J Exp Med. 2017;214(5):1371–1386.
  • Wu RC, Wang TL, Shih IM. The emerging roles of ARID1A in tumor suppression. Cancer Biol Ther. 2014 Jun 1;15(6):655–664.
  • McKinney M, Moffitt AB, Gaulard P, et al. The Genetic Basis of Hepatosplenic T-cell Lymphoma. Cancer Discov. 2017;7(4):369–379.
  • Wang L, Ni X, Covington KR, et al. Genomic profiling of Sezary syndrome identifies alterations of key T cell signaling and differentiation genes. Nat Genet. 2015;47(12):1426–1434.
  • Jiang L, Gu ZH, Yan ZX, et al. Exome sequencing identifies somatic mutations of DDX3X in natural killer/T-cell lymphoma. Nat Genet. 2015;47(9):1061–1066.
  • Bhadury J, Nilsson LM, Muralidharan SV, et al. BET and HDAC inhibitors induce similar genes and biological effects and synergize to kill in Myc-induced murine lymphoma. Proc Natl Acad Sci USA. 2014;111(26):E2721–2730.
  • Yang X, Han H, De Carvalho DD, et al. Gene body methylation can alter gene expression and is a therapeutic target in cancer. Cancer Cell. 2014;26(4):577–590.
  • Morin RD, Johnson NA, Severson TM, et al. Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin. Nat Genet. 2010;42(2):181–185.
  • McCabe MT, Ott HM, Ganji G, et al. EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature. 2012;492(7427):108–112.
  • Lopez C, Bergmann AK, Paul U, et al. Genes encoding members of the JAK-STAT pathway or epigenetic regulators are recurrently mutated in T-cell prolymphocytic leukaemia. Br J Haematol. 2016;173(2):265–273.
  • Yan J, Li B, Lin B, et al. EZH2 phosphorylation by JAK3 mediates a switch to noncanonical function in natural killer/T-cell lymphoma. Blood. 2016;128(7):948–958.
  • de Mel S, Hue SS, Jeyasekharan AD, et al. Molecular pathogenic pathways in extranodal NK/T cell lymphoma. J Hematol Oncol. 2019;12(1):33.
  • Lu C, Ward PS, Kapoor GS, et al. IDH mutation impairs histone demethylation and results in a block to cell differentiation. Nature. 2012;483(7390):474–478.
  • Turcan S, Rohle D, Goenka A, et al. IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Nature. 2012;483(7390):479–483.
  • Jones PA, Issa JP, Baylin S. Targeting the cancer epigenome for therapy. Nat Rev Genet. 2016;17(10):630–641.
  • Kim YH, Bagot M, Pinter-Brown L, et al. Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2018;19(9):1192–1204.
  • Wada H, Tsuboi R, Kato Y, et al. Phase I and pharmacokinetic study of the oral histone deacetylase inhibitor vorinostat in Japanese patients with relapsed or refractory cutaneous T-cell lymphoma. J Dermatol. 2012;39(10):823–828.
  • Duvic M, Talpur R, Ni X, et al. Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell lymphoma (CTCL). Blood. 2007;109(1):31–39.
  • Maruyama D, Tobinai K, Ogura M, et al. Romidepsin in Japanese patients with relapsed or refractory peripheral T-cell lymphoma: a phase I/II and pharmacokinetics study. Int J Hematol. 2017;106(5):655–665.
  • Piekarz RL, Frye R, Turner M, et al. Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma. J Clin Oncol. 2009;27(32):5410–5417.
  • Piekarz RL, Frye R, Prince HM, et al. Phase 2 trial of romidepsin in patients with peripheral T-cell lymphoma. Blood. 2011;117(22):5827–5834.
  • Foss F, Advani R, Duvic M, et al. A Phase II trial of Belinostat (PXD101) in patients with relapsed or refractory peripheral or cutaneous T-cell lymphoma. Br J Haematol. 2015;168(6):811–819.
  • McClure JJ, Li X, Chou CJ. Advances and Challenges of HDAC Inhibitors in Cancer Therapeutics. Adv Cancer Res. 2018;138:183–211.
  • Ageberg M, Rydström K, Relander T, et al. The histone deacetylase inhibitor valproic acid sensitizes diffuse large B-cell lymphoma cell lines to CHOP-induced cell death. Am J Transl Res. 2013;5(2):170–183.
  • Buglio D, Georgakis GV, Hanabuchi S, et al. Vorinostat inhibits STAT6-mediated TH2 cytokine and TARC production and induces cell death in Hodgkin lymphoma cell lines. Blood. 2008;112(4):1424–1433.
  • Garrido Castro P, van Roon EHJ, Pinhancos SS, et al. The HDAC inhibitor panobinostat (LBH589) exerts in vivo anti-leukaemic activity against MLL-rearranged acute lymphoblastic leukaemia and involves the RNF20/RNF40/WAC-H2B ubiquitination axis. Leukemia. 2018;32(2):323–331.
  • Kewitz S, Volkmer I, Staege MS. Curcuma Contra Cancer? Curcumin and Hodgkin’s Lymphoma. Cancer Growth Metastasis. 2013 Aug 8;6:35–52.
  • Klein JM, Henke A, Sauer M, et al. The histone deacetylase inhibitor LBH589 (panobinostat) modulates the crosstalk of lymphocytes with Hodgkin lymphoma cell lines. PLoS One. 2013;8(11):e79502.
  • Kretzner L, Scuto A, Dino PM, et al. Combining histone deacetylase inhibitor vorinostat with aurora kinase inhibitors enhances lymphoma cell killing with repression of c-Myc, hTERT, and micro-RNA levels. Cancer Res. 2011;71(11):3912–3920.
  • Rozati S, Cheng PF, Widmer DS, et al. Azacitidine Synergize in their Epigenetic Modulatory Effects to Induce Apoptosis in CTCL. Clin Cancer Res. 2016;22(8):2020–2031.
  • Mervis JS, McGee JS. Epigenetic therapy and dermatologic disease: moving beyond CTCL. J Dermatolog Treat. 2019;30(1):68–73.
  • Conti C, Leo E, Eichler GS, et al. Inhibition of histone deacetylase in cancer cells slows down replication forks, activates dormant origins, and induces DNA damage. Cancer Res. 2010;70(11):4470–4480.
  • Piekarz RL, Robey RW, Zhan Z, et al. T-cell lymphoma as a model for the use of histone deacetylase inhibitors in cancer therapy: impact of depsipeptide on molecular markers, therapeutic targets, and mechanisms of resistance. Blood. 2004;103(12):4636–4643.
  • Valdez BC, Brammer JE, Li Y, et al. Romidepsin targets multiple survival signaling pathways in malignant T cells. Blood Cancer J. 2015 Oct 16;5:e357.
  • Zhang C, Richon V, Ni X, et al. Selective induction of apoptosis by histone deacetylase inhibitor SAHA in cutaneous T-cell lymphoma cells: relevance to mechanism of therapeutic action. J Invest Dermatol. 2005;125(5):1045–1052.
  • Bates SE, Eisch R, Ling A, et al. Romidepsin in peripheral and cutaneous T-cell lymphoma: mechanistic implications from clinical and correlative data. Br J Haematol. 2015;170(1):96–109.
  • Ellis L, Pan Y, Smyth GK, et al. Histone deacetylase inhibitor panobinostat induces clinical responses with associated alterations in gene expression profiles in cutaneous T-cell lymphoma. Clin Cancer Res. 2008;14(14):4500–4510.
  • Moskowitz AJ, Horwitz SM. Targeting histone deacetylases in T-cell lymphoma. Leuk Lymphoma. 2017;58(6):1306–1319.
  • Coiffier B, Pro B, Prince HM, et al. Results from a pivotal, open-label, phase II study of romidepsin in relapsed or refractory peripheral T-cell lymphoma after prior systemic therapy. J Clin Oncol. 2012;30(6):631–636.
  • O’Connor OA, Horwitz S, Masszi T, et al. Belinostat in patients with relapsed or refractory peripheral t-cell lymphoma: Results of the pivotal phase II BELIEF (CLN-19) study. J Clin Oncol. 2015;33(23):2492–2499.
  • Olsen EA, Kim YH, Kuzel TM, et al. Phase IIb multicenter trial of vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma. J Clin Oncol. 2007;25(21):3109–3115.
  • San-Miguel JF, Hungria VT, Yoon SS, et al. Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial. Lancet Oncol. 2014;15(11):1195–1206.
  • Whittaker SJ, Demierre MF, Kim EJ, et al. Final results from a multicenter, international, pivotal study of romidepsin in refractory cutaneous T-cell lymphoma. J Clin Oncol. 2010;28(29):4485–4491.
  • Pro B, Horwitz SM, Prince HM, et al. Romidepsin induces durable responses in patients with relapsed or refractory angioimmunoblastic T-cell lymphoma. Hematol Oncol. 2017 Dec;35(4):914-917.
  • Duvic M, Dummer R, Becker JC, et al. Panobinostat activity in both bexarotene-exposed and -naive patients with refractory cutaneous T-cell lymphoma: results of a phase II trial. Eur J Cancer. 2013;49(2):386–394.
  • Shi Y, Dong M, Hong X, et al. Results from a multicenter, open-label, pivotal phase II study of chidamide in relapsed or refractory peripheral T-cell lymphoma. Ann Oncol. 2015;26(8):1766–1771.
  • Assouline SE, Nielsen TH, Yu S, et al. Phase 2 study of panobinostat with or without rituximab in relapsed diffuse large B-cell lymphoma. Blood. 2016;128(2):185–194.
  • Batlevi CL, Kasamon Y, Bociek RG, et al. ENGAGE- 501: phase II study of entinostat (SNDX-275) in relapsed and refractory Hodgkin lymphoma. Haematologica. 2016 Aug;101(8):968–975.
  • Child F, Ortiz-Romero PL, Alvarez R, et al. Phase II multicentre trial of oral quisinostat, a histone deacetylase inhibitor, in patients with previously treated stage IB-IVA mycosis fungoides/Sezary syndrome. Br J Dermatol. 2016;175(1):80–88.
  • Ribrag V, Kim WS, Bouabdallah R, et al. Safety and efficacy of abexinostat, a pan-histone deacetylase inhibitor, in non-Hodgkin lymphoma and chronic lymphocytic leukemia: results of a phase II study. Haematologica. 2017;102(5):903–909.
  • Dedes KJ, Dedes I, Imesch P, et al. Acquired vorinostat resistance shows partial cross-resistance to ‘second-generation’ HDAC inhibitors and correlates with loss of histone acetylation and apoptosis but not with altered HDAC and HAT activities. Anticancer Drugs. 2009;20(5):321–333.
  • Hu B, Younes A, Westin JR, et al. Phase-I and randomized phase-II trial of panobinostat in combination with ICE (ifosfamide, carboplatin, etoposide) in relapsed or refractory classical Hodgkin lymphoma. Leuk Lymphoma. 2018;59(4):863–870.
  • Budde LE, Zhang MM, Shustov AR, et al. A phase I study of pulse high-dose vorinostat (V) plus rituximab (R), ifosphamide, carboplatin, and etoposide (ICE) in patients with relapsed lymphoma. Br J Haematol. 2013;161(2):183–191.
  • Chihara D, Oki Y, Westin JR, et al. High response rate of romidepsin in combination with ICE (Ifosfamide, Carboplatin and Etoposide) in patients with relapsed or refractory peripheral T-cell lymphoma: Updates of phase i trial. Blood. 2015;126:3987.
  • Dupuis J, Morschhauser F, Ghesquieres H, et al. Combination of romidepsin with cyclophosphamide, doxorubicin, vincristine, and prednisone in previously untreated patients with peripheral T-cell lymphoma: a non-randomised, phase 1b/2 study. Lancet Haematol. 2015;2(4):e160–165.
  • Ganai SA. Histone deacetylase inhibitors modulating non-epigenetic players: The novel mechanism for small molecule based therapeutic intervention. Curr Drug Targets. 2018;19(6):593–601.
  • Narita T, Weinert BT, Choudhary C. Functions and mechanisms of non-histone protein acetylation. Nat Rev Mol Cell Biol. 2019;20(3):156–174.
  • Zhang Q, Wang S, Chen J, et al. (HDACs) guided novel therapies for T-cell lymphomas. Int J Med Sci. 2019;16(3):424–442.
  • Rodriguez-Gonzalez A, Lin T, Ikeda AK, et al. Role of the aggresome pathway in cancer: targeting histone deacetylase 6-dependent protein degradation. Cancer Res. 2008;68(8):2557–2560.
  • Cortiguera MG, Garcia-Gaipo L, Wagner SD, et al. Suppression of BCL6 function by HDAC inhibitor mediated acetylation and chromatin modification enhances BET inhibitor effects in B-cell lymphoma cells. Sci Rep. 2019;9(1):16495.
  • Wagner T, Brand P, Heinzel T, et al. Histone deacetylase 2 controls p53 and is a critical factor in tumorigenesis. Biochim Biophys Acta. 2014;1846(2):524–538.
  • Nalawansha DA, Zhang Y, Herath K, et al. HDAC1 substrate profiling using proteomics-based substrate trapping. ACS Chem Biol. 2018;13(12):3315–3324.
  • Lemonnier F, Dupuis J, Sujobert P, et al. Treatment with 5-azacytidine induces a sustained response in patients with angioimmunoblastic T-cell lymphoma. Blood. 2018;132(21):2305–2309.
  • Magic Z, Supic G, Brankovic-Magic M. Towards targeted epigenetic therapy of cancer. J Buon. 2009;14(Suppl 1):S79–88.
  • Brueckner B, Garcia Boy R, Siedlecki P, et al. Epigenetic reactivation of tumor suppressor genes by a novel small-molecule inhibitor of human DNA methyltransferases. Cancer Res. 2005;65(14):6305–6311.
  • O’Connor OA, Falchi L, Lue JK, et al. Oral 5-azacytidine and romidepsin exhibit marked activity in patients with PTCL: a multicenter phase 1 study. Blood. 2019;134(17):1395–1405.
  • Peters SL, Hlady RA, Opavska J, et al. Essential role for Dnmt1 in the prevention and maintenance of MYC-induced T-cell lymphomas. Mol Cell Biol. 2013;33(21):4321–4333.
  • Haney SL, Upchurch GM, Opavska J, et al. Dnmt3a is a haploinsufficient tumor suppressor in CD8+ peripheral T cell lymphoma. PLoS Genet. 2016;12(9):e1006334.
  • Shortt J, Ott CJ, Johnstone RW, et al. A chemical probe toolbox for dissecting the cancer epigenome. Nat Rev Cancer. 2017;17(3):160–183.
  • Panfil AR, Al-Saleem J, Howard CM, et al. PRMT5 is upregulated in HTLV-1-mediated T-cell transformation and selective inhibition alters viral gene expression and infected cell survival. Viruses. 2015 Dec 30;8(1). pii: E7.
  • Li Y, Chitnis N, Nakagawa H, et al. PRMT5 is required for lymphomagenesis triggered by multiple oncogenic drivers. Cancer Discov. 2015;5(3):288–303.
  • Nguyen TB, Sakata-Yanagimoto M, Asabe Y, et al. Identification of cell-type-specific mutations in nodal T-cell lymphomas. Blood Cancer J. 2017 Jan 6;7(1):e516.
  • Sakata-Yanagimoto M, Enami T, Yoshida K, et al. Somatic RHOA mutation in angioimmunoblastic T cell lymphoma. Nat Genet. 2014;46(2):171–175.
  • Lemonnier F, Cairns RA, Inoue S, et al. The IDH2 R172K mutation associated with angioimmunoblastic T-cell lymphoma produces 2HG in T cells and impacts lymphoid development. Proc Natl Acad Sci U S A. 2016;113(52):15084–15089.
  • DiNardo CD, Stein EM, de Botton S, et al. Durable remissions with ivosidenib in IDH1-mutated relapsed or refractory AML. N Engl J Med. 2018;378(25):2386–2398.
  • Stein EM, DiNardo CD, Pollyea DA, et al. Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood. 2017;130(6):722–731.
  • Fathi AT, DiNardo CD, Kline I, et al. Differentiation syndrome associated with enasidenib, a selective inhibitor of mutant isocitrate dehydrogenase 2: analysis of a Phase 1/2 Study. JAMA Oncol. 2018;4(8):1106–1110.
  • Intlekofer AM, Shih AH, Wang B, et al. Acquired resistance to IDH inhibition through trans or cis dimer-interface mutations. Nature. 2018;559(7712):125–129.
  • Perez-Salvia M, Esteller M. Bromodomain inhibitors and cancer therapy: from structures to applications. Epigenetics. 2017;12(5):323–339.
  • Yang Z, Yik JH, Chen R, et al. Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4. Mol Cell. 2005;19(4):535–545.
  • Filippakopoulos P, Qi J, Picaud S, et al. Selective inhibition of BET bromodomains. Nature. 2010;468(7327):1067–1073.
  • Abedin SM, Boddy CS, Munshi HG. BET inhibitors in the treatment of hematologic malignancies: current insights and future prospects. Onco Targets Ther. 2016;9:5943–5953.
  • Kim SR, Lewis JM, Cyrenne BM, et al. BET inhibition in advanced cutaneous T cell lymphoma is synergistically potentiated by BCL2 inhibition or HDAC inhibition. Oncotarget. 2018;9(49):29193–29207.
  • Zhao L, Okhovat JP, Hong EK, et al. Preclinical studies support combined inhibition of BET family proteins and histone deacetylases as epigenetic therapy for cutaneous t-cell lymphoma. Neoplasia. 2019;21(1):82–92.
  • Luchtel RA, Zimmermann MT, Hu G, et al. Recurrent MSC (E116K) mutations in ALK-negative anaplastic large cell lymphoma. Blood. 2019;133(26):2776–2789.
  • Dimopoulos MA, Tedeschi A, Trotman J, et al. Phase 3 trial of ibrutinib plus rituximab in waldenstrom’s macroglobulinemia. N Engl J Med. 2018;378(25):2399–2410.
  • Gregory GP, Dickinson M, Yannakou CK, et al. Rapid and durable complete remission of refractory AITL with azacitidine treatment in absence of TET2 mutation or concurrent MDS. Hemasphere. 2019;3(2):e187.
  • O’Connor OA, Bhagat G, Ganapathi K, et al. Changing the paradigms of treatment in peripheral T-cell lymphoma: from biology to clinical practice. Clin Cancer Res. 2014;20(20):5240–5254.
  • Luchtel RA, Dasari S, Oishi N, et al. Molecular profiling reveals immunogenic cues in anaplastic large cell lymphomas with DUSP22 rearrangements. Blood. 2018;132(13):1386–1398.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.