New directions in treating peripheral T-cell lymphomas (PTCL): leveraging epigenetic modifiers alone and in combination

References

• The Non-Hodgkin’s Lymphoma Classification Project. A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin’s lymphoma. Blood. 1997:89(11):3909–3918.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Vose J, Armitage J, Weisenburger D, et al. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol. 2008;26(25):4124–4130.
   PubMed Web of Science ®Google Scholar
• Ellin F, Landstrom J, Jerkeman M, et al. Real-world data on prognostic factors and treatment in peripheral T-cell lymphomas: a study from the Swedish Lymphoma Registry. Blood. 2014;124(10):1570–1577.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Fisher RI, Gaynor ER, Dahlberg S, et al. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin’s lymphoma. N Engl J Med. 1993;328(14):1002–1006.
   PubMed Web of Science ®Google Scholar
• Mak V, Hamm J, Chhanabhai M, et al. Survival of patients with peripheral T-cell lymphoma after first relapse or progression: spectrum of disease and rare long-term survivors. J Clin Oncol. 2013;31(16):1970–1976.
   PubMed Web of Science ®Google Scholar
• Horwitz S, O’Connor OA, Pro B, et al. Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Lancet. 2018.
   Web of Science ®Google Scholar
• Saillard C, Guermouche H, Derrieux C, et al. Response to 5-azacytidine in a patient with TET2-mutated angioimmunoblastic T-cell lymphoma and chronic myelomonocytic leukaemia preceded by an EBV-positive large B-cell lymphoma. Hematol Oncol. 2017;35(4):864–868.
   PubMed Web of Science ®Google Scholar
• Horwitz SM, Soto J, Youssoufian H, et al. The PRIMO study: A phase 2 study of duvelisib efficacy and safety in patients with relapsed or refractory peripheral t-cell lymphoma (PTCL. J Clin Oncol. 2018;36(15_suppl):TPS7590.
   Web of Science ®Google Scholar
• Toner LE, Vrhovac R, Smith EA, et al. The schedule-dependent effects of the novel antifolate pralatrexate and gemcitabine are superior to methotrexate and cytarabine in models of human non-Hodgkin’s lymphoma. Clin Cancer Res. 2006;12(3):924–932.
   PubMed Web of Science ®Google Scholar
• Kalac M, Scotto L, Marchi E, et al. HDAC inhibitors and decitabine are highly synergistic and associated with unique gene-expression and epigenetic profiles in models of DLBCL. Blood. 2011;118(20):5506–5516.
   PubMed Web of Science ®Google Scholar
• Jain S, Jirau-Serrano X, Zullo KM, et al. Preclinical pharmacologic evaluation of pralatrexate and romidepsin confirms potent synergy of the combination in a murine model of human t-cell lymphoma. Clin Cancer Res. 2015;21(9):2096–2106.
   PubMed Web of Science ®Google Scholar
• Marchi E, Zullo KM, Amengual JE, et al. The combination of hypomethylating agents and histone deacetylase inhibitors produce marked synergy in preclinical models of T-cell lymphoma. Br J Haematol. 2015 Oct;171(2):215–226.
   PubMed Web of Science ®Google Scholar
• Zullo KM, Guo Y, Cooke L, et al. Aurora A kinase inhibition selectively synergizes with histone deacetylase inhibitor through cytokinesis failure in T-cell lymphoma. Clin Cancer Res. 2015;21(18):4097–4109.
   PubMed Web of Science ®Google Scholar
• Paoluzzi L, Scotto L, Marchi E, et al. Romidepsin and belinostat synergize the antineoplastic effect of bortezomib in mantle cell lymphoma. Clin Cancer Res. 2010;16(2):554–565.
   PubMed Web of Science ®Google Scholar
• Marchi E, Paoluzzi L, Scotto L, et al. Pralatrexate is synergistic with the proteasome inhibitor bortezomib in in vitro and in vivo models of T-cell lymphoid malignancies. Clin Cancer Res. 2010;16(14):3648–3658.
   PubMed Web of Science ®Google Scholar
• Iqbal J, Wright G, Wang C, et al. Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma. Blood. 2014;123(19):2915–2923.
   PubMed Web of Science ®Google Scholar
• Sandell RF, Boddicker RL, Feldman AL. Genetic Landscape and Classification of peripheral T cell lymphomas. Curr Oncol Rep. 2017;19(4):28.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Ji MM, Huang YH, Huang JY, et al. Histone modifier gene mutations in peripheral T-cell lymphoma not otherwise specified. Haematologica. 2018;103(4):679–687.
   PubMed Web of Science ®Google Scholar
• Shah UA, Chung EY, Giricz O, et al. North American ATLL has a distinct mutational and transcriptional profile and responds to epigenetic therapies. Blood. 2018;132(14):1507–1518.
   PubMed Web of Science ®Google Scholar
• He YF, Li BZ, Li Z, et al. Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science. 2011;333(6047):1303–1307.
   PubMed Web of Science ®Google Scholar
• Ito S, Shen L, Dai Q, et al. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science. 2011;333(6047):1300–1303.
   PubMed Web of Science ®Google Scholar
• Tahiliani M, Koh KP, Shen Y, et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science. 2009;324(5929):930–935.
   PubMed Web of Science ®Google Scholar
• Quivoron C, Couronne L, Della Valle V, et al. TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis. Cancer Cell. 2011;20(1):25–38.
   PubMed Web of Science ®Google Scholar
• Muto H, Sakata-Yanagimoto M, Nagae G, et al. Reduced TET2 function leads to T-cell lymphoma with follicular helper T-cell-like features in mice. Blood Cancer J. 2014;4:e264.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Couronne L, Bastard C, Bernard OA. TET2 and DNMT3A mutations in human T-cell lymphoma. N Engl J Med. 2012;366(1):95–96.
   PubMed Web of Science ®Google Scholar
• Nagata Y, Kontani K, Enami T, et al. Variegated RHOA mutations in adult T-cell leukemia/lymphoma. Blood. 2016;127(5):596–604.
   PubMed Web of Science ®Google Scholar
• Odejide O, Weigert O, Lane AA, et al. A targeted mutational landscape of angioimmunoblastic T-cell lymphoma. Blood. 2014;123(9):1293–1296.
   PubMed Web of Science ®Google Scholar
• Sakata-Yanagimoto M, Enami T, Yoshida K, et al. Somatic RHOA mutation in angioimmunoblastic T cell lymphoma. Nat Genet. 2014;46(2):171–175.
   PubMed Web of Science ®Google Scholar
• Cairns RA, Iqbal J, Lemonnier F, et al. IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma. Blood. 2012;119(8):1901–1903.
   PubMed Web of Science ®Google Scholar
• Dawlaty MM, Breiling A, Le T, et al. Loss of Tet enzymes compromises proper differentiation of embryonic stem cells. Dev Cell. 2014;29(1):102–111.
   PubMed Web of Science ®Google Scholar
• Williams K, Christensen J, Pedersen MT, et al. TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity. Nature. 2011;473(7347):343–348.
   PubMed Web of Science ®Google Scholar
• Wu H, D’Alessio AC, Ito S, et al. Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells. Nature. 2011;473(7347):389–393.
   PubMed Web of Science ®Google Scholar
• Lemonnier F, Poullot E, Dupuy A, et al. Loss of 5-hydroxymethylcytosine is a frequent event in peripheral T-cell lymphomas. Haematologica. 2018;103(3):e115–e118.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• de Mel S, Soon GS, Mok Y, et al. The genomics and molecular biology of natural killer/T-cell lymphoma: opportunities for translation. Int J Mol Sci. 2018;19:7.
   Web of Science ®Google Scholar
• Gu T, Lin X, Cullen SM, et al. DNMT3A and TET1 cooperate to regulate promoter epigenetic landscapes in mouse embryonic stem cells. Genome Biol. 2018;19(1):88.
   PubMedGoogle Scholar
• Yi S, Sun J, Qiu L, et al. Dual role of EZH2 in cutaneous anaplastic large cell lymphoma: promoting tumor cell survival and regulating tumor microenvironment. J Invest Dermatol. 2018;138(5):1126–1136.
   PubMed Web of Science ®Google Scholar
• 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. 2018 Apr 7. doi: 10.1097/PAI.0000000000000644. [Epub ahead of print].
   PubMedGoogle Scholar
• Ng SY, Brown L, Stevenson K, et al. RhoA G17V is sufficient to induce autoimmunity and promotes T-cell lymphomagenesis in mice. Blood. 2018;132(9):935–947.
   PubMed Web of Science ®Google Scholar
• Cortes JR, Ambesi-Impiombato A, Couronne L, et al. RHOA G17V induces t follicular helper cell specification and promotes lymphomagenesis. Cancer Cell. 2018;33(2):259–273. e257.
   PubMed Web of Science ®Google Scholar
• Yoo HY, Sung MK, Lee SH, et al. A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T cell lymphoma. Nat Genet. 2014;46(4):371–375.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Coiffier B, Pro B, Prince HM, et al. Romidepsin for the treatment of relapsed/refractory peripheral T-cell lymphoma: pivotal study update demonstrates durable responses. J Hematol Oncol. 2014;7:11.
   PubMed Web of Science ®Google Scholar
• Kim SJ, Kim JH, Ki CS, et al. Epstein-Barr virus reactivation in extranodal natural killer/T-cell lymphoma patients: a previously unrecognized serious adverse event in a pilot study with romidepsin. Ann Oncol. 2016;27(3):508–513.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• DeAngelo DJ, Spencer A, Bhalla KN, et al. Phase Ia/II, two-arm, open-label, dose-escalation study of oral panobinostat administered via two dosing schedules in patients with advanced hematologic malignancies. Leukemia. 2013;27(8):1628–1636.
   PubMed Web of Science ®Google Scholar
• Uenogawa K, Hatta Y, Arima N, et al. Azacitidine induces demethylation of p16INK4a and inhibits growth in adult T-cell leukemia/lymphoma. Int J Mol Med. 2011;28(5):835–839.
   PubMed Web of Science ®Google Scholar
• Delarue R, Dupuis J, Sujobert P, et al. Treatment with hypomethylating agent 5-azacytidine induces sustained response in angioimmunoblastic T Cell lymphomas. Blood. 2016;128(22):4164.
   Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• O’Connor OA, Pro B, Pinter-Brown L, et al. Pralatrexate in patients with relapsed or refractory peripheral T-cell lymphoma: results from the pivotal PROPEL study. J Clin Oncol. 2011;29(9):1182–1189.
   PubMed Web of Science ®Google Scholar
• O’Connor OA, Marchi E, Volinn W, et al. Strategy for assessing new drug value in orphan diseases: an international case match control analysis of the PROPEL study. JNCI Cancer Spectrum. 2018.
   Google Scholar
• Chihara D, Fanale MA, Miranda RN, et al. The survival outcome of patients with relapsed/refractory peripheral T-cell lymphoma-not otherwise specified and angioimmunoblastic T-cell lymphoma. Br J Haematol. 2017;176(5):750–758.
   PubMed Web of Science ®Google Scholar
• Fujisawa M, Chiba S, Sakata-Yanagimoto M. Recent progress in the understanding of angioimmunoblastic T-cell lymphoma. J Clin Exp Hematop. 2017;57(3):109–119.
   PubMed Web of Science ®Google Scholar
• Fujisawa M, Sakata-Yanagimoto M, Nishizawa S, et al. Activation of RHOA-VAV1 signaling in angioimmunoblastic T-cell lymphoma. Leukemia. 2018;32(3):694–702.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Lee SH, Kim JS, Kim J, et al. A highly recurrent novel missense mutation in CD28 among angioimmunoblastic T-cell lymphoma patients. Haematologica. 2015;100(12):e505–e507.
   PubMed Web of Science ®Google Scholar
• Manso R, Rodriguez-Pinilla SM, Gonzalez-Rincon J, et al. Recurrent presence of the PLCG1 S345F mutation in nodal peripheral T-cell lymphomas. Haematologica. 2015;100(1):e25–27.
   PubMed Web of Science ®Google Scholar
• Rohr J, Guo S, Huo J, et al. Recurrent activating mutations of CD28 in peripheral T-cell lymphomas. Leukemia. 2016;30(5):1062–1070.
   PubMed Web of Science ®Google Scholar
• Zinzani PL, Musuraca G, Tani M, et al. Phase II trial of proteasome inhibitor bortezomib in patients with relapsed or refractory cutaneous T-cell lymphoma. J Clin Oncol. 2007;25(27):4293–4297.
   PubMed Web of Science ®Google Scholar
• Tan D, Phipps C, Hwang WY, et al. Panobinostat in combination with bortezomib in patients with relapsed or refractory peripheral T-cell lymphoma: an open-label, multicentre phase 2 trial. Lancet Haematol. 2015;2(8):e326–333.
   PubMed Web of Science ®Google Scholar
• Gao M, Chen G, Wang H, et al. Therapeutic potential and functional interaction of carfilzomib and vorinostat in T-cell leukemia/lymphoma. Oncotarget. 2016;7(20):29102–29115.
   PubMedGoogle Scholar
• Foss F, Pro B, Miles Prince H, et al. Responses to romidepsin by line of therapy in patients with relapsed or refractory peripheral T-cell lymphoma. Cancer Med. 2017;6(1):36–44.
   PubMed Web of Science ®Google Scholar
• Amengual JE, Lichtenstein R, Lue J, et al. A phase I study of romidepsin and pralatrexate reveals marked activity in relapsed and refractory T-cell lymphoma. Blood. 2017;131(4):397–407.
   PubMedGoogle Scholar
• Lee SS, Jung SH, Ahn JS, et al. Pralatrexate in combination with bortezomib for relapsed or refractory peripheral T cell lymphoma in 5 elderly patients. J Korean Med Sci. 2016;31(7):1160–1163.
   PubMed Web of Science ®Google Scholar
• Barr PM, Li H, Spier C, et al. Phase II intergroup trial of alisertib in relapsed and refractory peripheral T-cell lymphoma and transformed mycosis fungoides: SWOG 1108. J Clin Oncol. 2015;33(21):2399–2404.
   PubMed Web of Science ®Google Scholar
• Oa O, Özcan M, Jacobsen ED, et al. First multicenter, randomized phase 3 study in patients (Pts) with relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL): alisertib (MLN8237) versus investigator’s choice (Lumiere trial; NCT01482962). Blood. 2015;126(23):341.
   Web of Science ®Google Scholar
• Park JH, Jong HS, Kim SG, et al. Inhibitors of histone deacetylases induce tumor-selective cytotoxicity through modulating Aurora-A kinase. J Mol Med (Berl). 2008;86(1):117–128.
   PubMed Web of Science ®Google Scholar
• Strati P, Yasuhiro O, Fayad LE, et al. A phase 1 trial of alisertib and romidepsin for relapsed/refractory aggressive B-cell and T-cell lymphomas. 2017;130(Suppl 1), 4074.
   Google Scholar
• Horwitz SM, Vose JM, Advani R, et al. Pralatrexate and gemcitabine in patients with relapsed or refractory lymphoproliferative malignancies: phase 1 Results. Blood. 2009;114(22):1674.
   Web of Science ®Google Scholar
• Falchi L, Lue JK, Montanari F, et al. Combined hypomethylating agents (HMA) and histone deacetylase inhibitors (HDACi) exhibit compelling activity in patients with peripheral t-cell lymphoma (PTCL) with high complete response rates in angioimmunoblastic T-cell lymphoma (AITL). American Society of Hematology Annual Meeting, San Diego, CA. Oral Abstract 1002. 2018.
   Google Scholar
• Dreyling M, Morschhauser F, Bouabdallah K, et al. Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma. Ann Oncol. 2017;28(9):2169–2178.
   PubMed Web of Science ®Google Scholar
• Flinn IW, O’Brien S, Kahl B, et al. Duvelisib, a novel oral dual inhibitor of PI3K-delta,gamma, is clinically active in advanced hematologic malignancies. Blood. 2018;131(8):877–887.
   PubMed Web of Science ®Google Scholar
• Horwitz SM, Koch R, Porcu P, et al. Activity of the PI3K-delta,gamma inhibitor duvelisib in a phase 1 trial and preclinical models of T-cell lymphoma. Blood. 2018;131(8):888–898.
   PubMed Web of Science ®Google Scholar
• Moskowitz A, Koch R, Mehta-Shah N, et al. In vitro, in vivo, and parallel phase i evidence support the safety and activity of duvelisib, a PI3K δ,γ inhibitor, in combination with romidepsin or bortezomib in relapsed/refractory T‐cell lymphoma. Blood. 2017;130(Suppl):1.
   PubMedGoogle Scholar
• Morschhauser F, Fitoussi O, Haioun C, et al. A phase 2, multicentre, single-arm, open-label study to evaluate the safety and efficacy of single-agent lenalidomide (Revlimid) in subjects with relapsed or refractory peripheral T-cell non-Hodgkin lymphoma: the EXPECT trial. Eur J Cancer. 2013;49(13):2869–2876.
   PubMed Web of Science ®Google Scholar
• Toumishey E, Prasad A, Dueck G, et al. Final report of a phase 2 clinical trial of lenalidomide monotherapy for patients with T-cell lymphoma. Cancer. 2015;121(5):716–723.
   PubMed Web of Science ®Google Scholar
• Zinzani PL, Pellegrini C, Broccoli A, et al. Lenalidomide monotherapy for relapsed/refractory peripheral T-cell lymphoma not otherwise specified. Leuk Lymphoma. 2011;52(8):1585–1588.
   PubMed Web of Science ®Google Scholar
• Cosenza M, Civallero M, Fiorcari S, et al. The histone deacetylase inhibitor romidepsin synergizes with lenalidomide and enhances tumor cell death in T-cell lymphoma cell lines. Cancer Biol Ther. 2016;17(10):1094–1106.
   PubMed Web of Science ®Google Scholar
• Mehta-Shah N, Lunning MA, Boruchov AM, et al. A phase I/II trial of the combination of romidepsin and lenalidomide in patients with relapsed/refractory lymphoma and myeloma: activity in T-cell lymphoma. J clin oncol. 2015;33(15_suppl):8521.
   Web of Science ®Google Scholar
• Mehta-Shah N, Moskowitz AJ, Lunning M, et al. A phase Ib/IIa trial of the combination of romidepsin, lenalidomide and carfilzomib in patients with relapsed/refractory lymphoma shows complete responses in relapsed and refractory T-cell lymphomas. Blood. 2016;128(22):2991.
   Web of Science ®Google Scholar
• Mehta-Shah N, Moskowitz AJ, Lunning MA, et al. A phase Ib/IIa trial of the combination of romidepsin, lenalidomide and carfilzomib in patients with relapsed/refractory lymphoma shows complete responses in relapsed and refractory B- and T-cell lymphomas. Blood. 2017;130(Suppl 1):821.
   Google Scholar
• Dupuis J, Morschhauser F, Ghesquieres H, et al. Final analysis of the RO-CHOP phase Ib/II Study: romidepsin in association with CHOP in patients with peripheral T-cell lymphoma (PTCL). Blood. 2014;124(21):504.
   Web of Science ®Google Scholar
• Delarue R, Zinzani PL, Hertzberg MS, et al. ROCHOP study: A phase III randomized study of CHOP compared to romidepsin-CHOP in untreated peripheral T-cell lymphoma. J Clin Oncol. 2017;31(15_suppl):TPS8616.
   Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Stein EM, DiNardo CD, Pollyea DA, et al. Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood. 2017;130(6):722–731.
   PubMed Web of Science ®Google Scholar
• Yamaguchi H, Hung MC. Regulation and Role of EZH2 in Cancer. Cancer Res Treat. 2014;46(3):209–222.
   PubMed Web of Science ®Google Scholar
• Shi M, Shahsafaei A, Liu C, et al. Enhancer of zeste homolog 2 is widely expressed in T-cell neoplasms, is associated with high proliferation rate and correlates with MYC and pSTAT3 expression in a subset of cases. Leuk Lymphoma. 2015;56(7):2087–2091.
   PubMed Web of Science ®Google Scholar
• Fujikawa D, Nakagawa S, Hori M, et al. Polycomb-dependent epigenetic landscape in adult T-cell leukemia. Blood. 2016;127(14):1790–1802.
   PubMed Web of Science ®Google Scholar
• Yamagishi M, Hori M, Fujikawa D, et al. Development and molecular analysis of synthetic lethality by targeting EZH1 and EZH2 in Non-Hodgkin lymphomas. Blood. 2016;128(22):462.
   Web of Science ®Google Scholar
• Yamagishi M, Fujikawa D, Honma D, et al. Polycomb-dependent epigenetic landscape in adult t cell leukemia (ATL); providing proof of concept for targeting EZH1/2 to selectively eliminate the HTLV-1 infected population. Blood. 2015;126(23):572.
   Web of Science ®Google Scholar
• Islam S, Vick E, Huber B, et al. Co-targeting aurora kinase with PD-L1 and PI3K abrogates immune checkpoint mediated proliferation in peripheral T-cell lymphoma: a novel therapeutic strategy. Oncotarget. 2017;8(59):100326–100338.
   PubMedGoogle Scholar
• O’Connor OA, Amengual J, Colbourn D, et al. Pralatrexate: a comprehensive update on pharmacology, clinical activity and strategies to optimize use. Leuk Lymphoma. 2017;58(11):2548–2557.
   PubMed Web of Science ®Google Scholar
• Amengual JE, Lichtenstein R, Lue J, et al. A phase 1 study of romidepsin and pralatrexate reveals marked activity in relapsed and refractory T-cell lymphoma. Blood. 2018;131(4):397–407.
   PubMed Web of Science ®Google Scholar