血管免疫母T细胞淋巴瘤发病机制及治疗进展
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摘要
血管免疫母T细胞淋巴瘤(angioimmunoblastic T-cell lymphoma,AITL)是外周T细胞淋巴瘤(peripheral T-cell lymphoma,PTCL)中较为常见的类型,其恶性细胞起源为滤泡辅助T细胞(follicular T helper cell,TFH)。近年来研究发现有较多基因突变与之发病相关,如TET2、DNMT3A、IDH2和RHOA等。治疗上以蒽环类化疗药物为基础的一线治疗效果欠佳,目前更多的研究关注于化疗与新药联合是否有助于提升疗效。随着对发病机制的深入研究,越来越多的靶点将成为潜在治疗药物的基础。
Angioimmunoblastic T-cell lymphoma(AITL) is one of the most common subtypes of peripheral T-cell lymphomas. It is a follicular T-helper-derived neoplasm, and characterized by the presence of some genetic alterations, such as mutations in TET2, DNMT3 A, IDH2, and RHOA. Anthracycline-containing regimens represent the most widely adopted first-line option; however, new biologic agents should be designed and incorporated to improve treatment response. The elucidation of the specific roles of these genetic alterations in AITL will facilitate the development of molecularly targeted therapies to treat this disease.
Angioimmunoblastic T-cell lymphoma(AITL) is one of the most common subtypes of peripheral T-cell lymphomas. It is a follicular T-helper-derived neoplasm, and characterized by the presence of some genetic alterations, such as mutations in TET2, DNMT3 A, IDH2, and RHOA. Anthracycline-containing regimens represent the most widely adopted first-line option; however, new biologic agents should be designed and incorporated to improve treatment response. The elucidation of the specific roles of these genetic alterations in AITL will facilitate the development of molecularly targeted therapies to treat this disease.
引文
[1]Vose J,Armitage J,Weisenburger D.International peripheral T-cell and natural killer/T-cell lymphoma study:pathology findings and clinical outcomes[J].J Clin Oncol,2008,26(25):4124-4130.
[2]Federico M,Rudiger T,Bellei M,et al.Clinicopathologic characteristics of angioimmunoblastic T-cell lymphoma:analysis of the international peripheral T-cell lymphoma project[J].J Clin Oncol,2013,31(2):240-246.
[3]Mourad N,Mounier N,Briere J,et al.Clinical,biologic,and pathologic features in 157 patients with angioimmunoblastic T-cell lymphoma treated within the Groupe d'Etude des Lymphomes de l'Adulte(GELA)trials[J].Blood,2008,111(9):4463-4470.
[4]Kim CH,Lim HW,Kim JR,et al.Unique gene expression program of human germinal center T helper cells[J].Blood,2004,104(7):1952-1960.
[5]Dupuis J,Boye K,Martin N,et al.Expression of CXCL13 by neoplastic cells in angioimmunoblastic T-cell lymphoma(AITL):a new diagnostic marker providing evidence that AITL derives from follicular helper T cells[J].Am J Surg Pathol,2006,30(4):490-494.
[6]Willenbrock K,Roers A,Seidl C,et al.Analysis of T-cell subpopulations in T-cell non-Hodgkin's lymphoma of angioimmunoblastic lymphadenopathy with dysproteinemia type by single target gene amplification of T cell receptor-beta gene rearrangements[J].Am J Pathol,2001,158(5):1851-1857.
[7]Willenbrock K,Renne C,Gaulard P,et al.In angioimmunoblastic T-cell lymphoma,neoplastic T cells may be a minor cell population.A molecular single-cell and immunohistochemical study[J].Virchows Arch,2005,446(1):15-20.
[8]Zhou Y,Attygalle AD,Chuang SS,et al.Angioimmunoblastic T-cell lymphoma:histological progression associates with EBV and HHV6B viral load[J].Br J Haematol,2007,138(1):44-53.
[9]Iqbal J,Weisenburger DD,Greiner TC,et al.Molecular signatures to improve diagnosis in peripheral T-cell lymphoma and prognostication in angioimmunoblastic T-cell lymphoma[J].Blood,2010,115(5):1026-1036.
[10]de Leval L,Rickman DS,Thielen C,et al.The gene expression profile of nodal peripheral T-cell lymphoma demonstrates a molecular link between angioimmunoblastic T-cell lymphoma(AITL)and follicular helper T(TFH)cells[J].Blood,2007,109(11):4952-4963.
[11]Piccaluga PP,Agostinelli C,Califano A,et al.Gene expression analysis of angioimmunoblastic lymphoma indicates derivation from T follicular helper cells and vascular endothelial growth factor deregulation[J].Cancer Res,2007,67(22):10703-10710.
[12]Jaffe AB,Hall A.Rho GTPases:biochemistry and biology[J].Annu Rev Cell Dev Biol,2005,(21):247-269.
[13]Boulter E,Estrach S,Garcia-Mata R,et al.Off the beaten paths:alternative and crosstalk regulation of Rho GTPases[J].FASEB J,2012,26(2):469-479.
[14]Ondrejka SL,Grzywacz B,Bodo J,et al.Angioimmunoblastic T-cell Lymphomas With the RHOA p.Gly17Val Mutation Have Classic Clinical and Pathologic Features[J].Am J Surg Pathol,2016,40(3):335-341.
[15]Manso R,Sanchez-Beato M,Monsalvo S,et al.The RHOA G17V gene mutation occurs frequently in peripheral T-cell lymphoma and is associated with a characteristic molecular signature[J].Blood,2014,123(18):2893-2894.
[16]Yoo HY,Sung MK,Lee S H,et al.A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T cell lymphoma[J].Nat Genet,2014,46(4):371-375.
[17]Sakata-Yanagimoto M,Enami T,Yoshida K,et al.Somatic RHOA mutation in angioimmunoblastic T cell lymphoma[J].Nat Genet,2014,46(2):171-175.
[18]Palomero T,Couronne L,Khiabanian H,et al.Recurrent mutations in epigenetic regulators,RHOA and FYN kinase in peripheral T cell lymphomas[J].Nat Genet,2014,46(2):166-170.
[19]Quivoron C,Couronne L,Della VV,et al.TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis[J].Cancer Cell,2011,20(1):25-38.
[20]Couronne L,Bastard C,Bernard OA.TET2 and DNMT3A mutations in human T-cell lymphoma[J].N Engl J Med,2012,366(1):95-96.
[21]Cairns RA,Iqbal J,Lemonnier F,et al.IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma[J].Blood,2012,119(8):1901-1903.
[22]Wang C,Mc Keithan TW,Gong Q,et al.IDH2R172 mutations define a unique subgroup of patients with angioimmunoblastic T-cell lymphoma[J].Blood,2015,126(15):1741-1752.
[23]Rasmussen KD,Jia G,Johansen JV,et al.Loss of TET2 in hematopoietic cells leads to DNA hypermethylation of active enhancers and induction of leukemogenesis[J].Genes Dev,2015,29(9):910-922.
[24]Couronne L,Bastard C,Bernard OA.TET2 and DNMT3A mutations in human T-cell lymphoma[J].N Engl J Med,2012,366(1):95-96.
[25]Xie M,Lu C,Wang J,et al.Age-related mutations associated with clonal hematopoietic expansion and malignancies[J].Nat Med,2014,20(12):1472-1478.
[26]Iqbal J,Wright G,Wang C,et al.Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma[J].Blood,2014,123(19):2915-2923.
[27]Rohr J,Guo S,Huo J,et al.Recurrent activating mutations of CD28 in peripheral T-cell lymphomas[J].Leukemia,2016,30(5):1062-1070.
[28]Wilhelm M,Smetak M,Reimer P,et al.First-line therapy of peripheral T-cell lymphoma:extension and long-term follow-up of a study investigating the role of autologous stem cell transplantation[J].Blood Cancer J,2016,6(7):e452.
[29]D'Amore F,Relander T,Lauritzsen GF,et al.Up-front autologous stemcell transplantation in peripheral T-cell lymphoma:NLG-T-01[J].J Clin Oncol,2012,30(25):3093-3099.
[30]Schetelig J,Fetscher S,Reichle A,et al.Long-term disease-free survival in patients with angioimmunoblastic T-cell lymphoma after high-dose chemotherapy and autologous stem cell transplantation[J].Haematologica,2003,88(11):1272-1278.
[31]Kyriakou C,Canals C,Goldstone A,et al.High-dose therapy and autologous stem-cell transplantation in angioimmunoblastic lymphoma:complete remission at transplantation is the major determinant of outcome-lymphoma working party of the European group for blood and marrow transplantation[J].J Clin Oncol,2008,26(2):218-224.
[32]Abouyabis AN,Shenoy PJ,Sinha R,et al.A systematic review and metaanalysis of front-line anthracycline-based chemotherapy regimens for peripheral T-Cell lymphoma[J].ISRN Hematol,2011,(2011):623924.
[33]Briski R,Feldman AL,Bailey NG,et al.The role of front-line anthracycline-containing chemotherapy regimens in peripheral T-cell lymphomas[J].Blood Cancer J,2014,4(5):e214.
[34]Schmitz N,Trumper L,Ziepert M,et al.Treatment and prognosis of mature T-cell and NK-cell lymphoma:an analysis of patients with T-cell lymphoma treated in studies of the German high-grade non-Hodgkin lymphoma study group[J].Blood,2010,116(18):3418-3425.
[35]Advani R,Horwitz S,Zelenetz A,et al.Angioimmunoblastic T cell lymphoma:treatment experience with cyclosporine[J].Leuk Lymph,2007,48(3):521-525.
[36]Delfau-Larue MH,de Leval L,Joly B,et al.Targeting intratumoral B cells with rituximab in addition to CHOP in angioimmunoblastic T-cell lymphoma.A clinicobiological study of the GELA[J].Haematol,2012,97(10):1594-1602.
[37]Ganjoo K,Hong F,Horning SJ,et al.Bevacizumab and cyclosphosphamide,doxorubicin,vincristine and prednisone in combination for patients with peripheral T-cell or natural killer cell neoplasms:an eastern cooperative oncology group study(E2404)[J].Leuk Lymph,2014,55(4):768-772.
[38]Kluin-Nelemans HC,van Marwijk KM,Lugtenburg PJ,et al.Intensified alemtuzumab-CHOP therapy for peripheral T-cell lymphoma[J].Ann Oncol,2011,22(7):1595-1600.
[39]Kim SJ,Yoon DH,Kang HJ,et al.Bortezomib in combination with CHOP as first-line treatment for patients with stageⅢ/Ⅳperipheral T-cell lymphomas:a multicentre,single-arm,phase 2 trial[J].Eur J Cancer,2012,48(17):3223-3231.
[40]Foss FM,Sjak-Shie N,Goy A,et al.A multicenter phaseⅡtrial to determine the safety and efficacy of combination therapy with denileukin diftitox and cyclophosphamide,doxorubicin,vincristine and prednisone in untreated peripheral T-cell lymphoma:the CONCEPT study[J].Leuk Lymph,2013,54(7):1373-1379.
[41]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].J Clin Oncol,2013,31(16):1970-1976.
[42]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].J Clin Oncol,2011,29(9):1182-1189.
[43]Piekarz RL,Frye R,Prince HM,et al.PhaseⅡtrial of romidepsin in patients with peripheral T-cell lymphoma[J].Blood,2011,117(22):5827-5834.
[44]O'Connor OA,Horwitz S,Masszi T,et al.Belinostat in patients with relapsed or refractory peripheral T-cell lymphoma:results of the pivotal phaseⅡBELIEF(CLN-19)Study[J].J Clin Oncol,2015,33(23):2492-2499.
[45]Shi Y,Jia B,Xu W,et al.Chidamide in relapsed or refractory peripheral T cell lymphoma:a multicenter real-world study in China[J].J Hematol Oncol,2017,10(1):69.
[46]D'Amore F,Radford J,Relander T,et al.PhaseⅡtrial of zanolimumab(Hu Max-CD4)in relapsed or refractory non-cutaneous peripheral T cell lymphoma[J].Br J Haematol,2010,150(5):565-573.
[47]Dang NH,Pro B,Hagemeister FB,et al.PhaseⅡtrial of denileukin diftitox for relapsed/refractory T-cell non-Hodgkin lymphoma[J].Br J Haematol,2007,136(3):439-447.
[48]Cerchietti L,Melnick A.Targeting BCL6 in diffuse large B-cell lymphoma:what does this mean for the future treatment[J]?Exp Rev Hematol,2013,6(4):343-345.
[49]Dupont T,Yang SN,Patel J,et al.Selective targeting of BCL6 induces oncogene addiction switching to BCL2 in B-cell lymphoma[J].Oncotarget,2016,7(3):3520-3532.
[50]Platt AM,Gibson VB,Patakas A,et al.Abatacept limits breach of selftolerance in a murine model of arthritis via effects on the generation of T follicular helper cells[J].J Immunol,2010,185(3):1558-1567.
[51]Yang Q,Modi P,Newcomb T,et al.Idelalisib:first-in-class PI3K delta inhibitor for the treatment of chronic lymphocytic leukemia,small lymphocytic leukemia,and follicular lymphoma[J].Clin Cancer Res,2015,21(7):1537-1542.
[52]Chavele KM,Merry E,Ehrenstein MR.Cutting edge:circulating plasmablasts induce the differentiation of human T follicular helper cells via IL-6 production[J].J Immunol,2015,194(6):2482-2485.
[53]Hong D,Kurzrock R,Kim Y,et al.AZD9150,a next-generation antisense oligonucleotide inhibitor of STAT3 with early evidence of clinical activity in lymphoma and lung cancer[J].Sci Transl Med,2015,7(314):185-314.
[54]Klimatcheva E,Pandina T,Reilly C,et al.CXCL13 antibody for the treatment of autoimmune disorders[J].BMC Immunol,2015,16(1):6.
[55]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[J].Hematol Oncol,2017,35(4):864.
[56]Cheminant M,Bruneau J,Kosmider O,et al.Efficacy of 5-azacytidine in a TET2 mutated angioimmunoblastic T cell lymphoma[J].Br J Haematol,2015,168(6):913-916.
[57]Bejar R,Lord A,Stevenson K,et al.TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients[J].Blood,2014,124(17):2705-2712.
[58]Stein EM,Di Nardo CD,Pollyea DA,et al.Enasidenib in mutant IDH2relapsed or refractory acute myeloid leukemia[J].Blood,2017,130(6):722-731.
[2]Federico M,Rudiger T,Bellei M,et al.Clinicopathologic characteristics of angioimmunoblastic T-cell lymphoma:analysis of the international peripheral T-cell lymphoma project[J].J Clin Oncol,2013,31(2):240-246.
[3]Mourad N,Mounier N,Briere J,et al.Clinical,biologic,and pathologic features in 157 patients with angioimmunoblastic T-cell lymphoma treated within the Groupe d'Etude des Lymphomes de l'Adulte(GELA)trials[J].Blood,2008,111(9):4463-4470.
[4]Kim CH,Lim HW,Kim JR,et al.Unique gene expression program of human germinal center T helper cells[J].Blood,2004,104(7):1952-1960.
[5]Dupuis J,Boye K,Martin N,et al.Expression of CXCL13 by neoplastic cells in angioimmunoblastic T-cell lymphoma(AITL):a new diagnostic marker providing evidence that AITL derives from follicular helper T cells[J].Am J Surg Pathol,2006,30(4):490-494.
[6]Willenbrock K,Roers A,Seidl C,et al.Analysis of T-cell subpopulations in T-cell non-Hodgkin's lymphoma of angioimmunoblastic lymphadenopathy with dysproteinemia type by single target gene amplification of T cell receptor-beta gene rearrangements[J].Am J Pathol,2001,158(5):1851-1857.
[7]Willenbrock K,Renne C,Gaulard P,et al.In angioimmunoblastic T-cell lymphoma,neoplastic T cells may be a minor cell population.A molecular single-cell and immunohistochemical study[J].Virchows Arch,2005,446(1):15-20.
[8]Zhou Y,Attygalle AD,Chuang SS,et al.Angioimmunoblastic T-cell lymphoma:histological progression associates with EBV and HHV6B viral load[J].Br J Haematol,2007,138(1):44-53.
[9]Iqbal J,Weisenburger DD,Greiner TC,et al.Molecular signatures to improve diagnosis in peripheral T-cell lymphoma and prognostication in angioimmunoblastic T-cell lymphoma[J].Blood,2010,115(5):1026-1036.
[10]de Leval L,Rickman DS,Thielen C,et al.The gene expression profile of nodal peripheral T-cell lymphoma demonstrates a molecular link between angioimmunoblastic T-cell lymphoma(AITL)and follicular helper T(TFH)cells[J].Blood,2007,109(11):4952-4963.
[11]Piccaluga PP,Agostinelli C,Califano A,et al.Gene expression analysis of angioimmunoblastic lymphoma indicates derivation from T follicular helper cells and vascular endothelial growth factor deregulation[J].Cancer Res,2007,67(22):10703-10710.
[12]Jaffe AB,Hall A.Rho GTPases:biochemistry and biology[J].Annu Rev Cell Dev Biol,2005,(21):247-269.
[13]Boulter E,Estrach S,Garcia-Mata R,et al.Off the beaten paths:alternative and crosstalk regulation of Rho GTPases[J].FASEB J,2012,26(2):469-479.
[14]Ondrejka SL,Grzywacz B,Bodo J,et al.Angioimmunoblastic T-cell Lymphomas With the RHOA p.Gly17Val Mutation Have Classic Clinical and Pathologic Features[J].Am J Surg Pathol,2016,40(3):335-341.
[15]Manso R,Sanchez-Beato M,Monsalvo S,et al.The RHOA G17V gene mutation occurs frequently in peripheral T-cell lymphoma and is associated with a characteristic molecular signature[J].Blood,2014,123(18):2893-2894.
[16]Yoo HY,Sung MK,Lee S H,et al.A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T cell lymphoma[J].Nat Genet,2014,46(4):371-375.
[17]Sakata-Yanagimoto M,Enami T,Yoshida K,et al.Somatic RHOA mutation in angioimmunoblastic T cell lymphoma[J].Nat Genet,2014,46(2):171-175.
[18]Palomero T,Couronne L,Khiabanian H,et al.Recurrent mutations in epigenetic regulators,RHOA and FYN kinase in peripheral T cell lymphomas[J].Nat Genet,2014,46(2):166-170.
[19]Quivoron C,Couronne L,Della VV,et al.TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis[J].Cancer Cell,2011,20(1):25-38.
[20]Couronne L,Bastard C,Bernard OA.TET2 and DNMT3A mutations in human T-cell lymphoma[J].N Engl J Med,2012,366(1):95-96.
[21]Cairns RA,Iqbal J,Lemonnier F,et al.IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma[J].Blood,2012,119(8):1901-1903.
[22]Wang C,Mc Keithan TW,Gong Q,et al.IDH2R172 mutations define a unique subgroup of patients with angioimmunoblastic T-cell lymphoma[J].Blood,2015,126(15):1741-1752.
[23]Rasmussen KD,Jia G,Johansen JV,et al.Loss of TET2 in hematopoietic cells leads to DNA hypermethylation of active enhancers and induction of leukemogenesis[J].Genes Dev,2015,29(9):910-922.
[24]Couronne L,Bastard C,Bernard OA.TET2 and DNMT3A mutations in human T-cell lymphoma[J].N Engl J Med,2012,366(1):95-96.
[25]Xie M,Lu C,Wang J,et al.Age-related mutations associated with clonal hematopoietic expansion and malignancies[J].Nat Med,2014,20(12):1472-1478.
[26]Iqbal J,Wright G,Wang C,et al.Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma[J].Blood,2014,123(19):2915-2923.
[27]Rohr J,Guo S,Huo J,et al.Recurrent activating mutations of CD28 in peripheral T-cell lymphomas[J].Leukemia,2016,30(5):1062-1070.
[28]Wilhelm M,Smetak M,Reimer P,et al.First-line therapy of peripheral T-cell lymphoma:extension and long-term follow-up of a study investigating the role of autologous stem cell transplantation[J].Blood Cancer J,2016,6(7):e452.
[29]D'Amore F,Relander T,Lauritzsen GF,et al.Up-front autologous stemcell transplantation in peripheral T-cell lymphoma:NLG-T-01[J].J Clin Oncol,2012,30(25):3093-3099.
[30]Schetelig J,Fetscher S,Reichle A,et al.Long-term disease-free survival in patients with angioimmunoblastic T-cell lymphoma after high-dose chemotherapy and autologous stem cell transplantation[J].Haematologica,2003,88(11):1272-1278.
[31]Kyriakou C,Canals C,Goldstone A,et al.High-dose therapy and autologous stem-cell transplantation in angioimmunoblastic lymphoma:complete remission at transplantation is the major determinant of outcome-lymphoma working party of the European group for blood and marrow transplantation[J].J Clin Oncol,2008,26(2):218-224.
[32]Abouyabis AN,Shenoy PJ,Sinha R,et al.A systematic review and metaanalysis of front-line anthracycline-based chemotherapy regimens for peripheral T-Cell lymphoma[J].ISRN Hematol,2011,(2011):623924.
[33]Briski R,Feldman AL,Bailey NG,et al.The role of front-line anthracycline-containing chemotherapy regimens in peripheral T-cell lymphomas[J].Blood Cancer J,2014,4(5):e214.
[34]Schmitz N,Trumper L,Ziepert M,et al.Treatment and prognosis of mature T-cell and NK-cell lymphoma:an analysis of patients with T-cell lymphoma treated in studies of the German high-grade non-Hodgkin lymphoma study group[J].Blood,2010,116(18):3418-3425.
[35]Advani R,Horwitz S,Zelenetz A,et al.Angioimmunoblastic T cell lymphoma:treatment experience with cyclosporine[J].Leuk Lymph,2007,48(3):521-525.
[36]Delfau-Larue MH,de Leval L,Joly B,et al.Targeting intratumoral B cells with rituximab in addition to CHOP in angioimmunoblastic T-cell lymphoma.A clinicobiological study of the GELA[J].Haematol,2012,97(10):1594-1602.
[37]Ganjoo K,Hong F,Horning SJ,et al.Bevacizumab and cyclosphosphamide,doxorubicin,vincristine and prednisone in combination for patients with peripheral T-cell or natural killer cell neoplasms:an eastern cooperative oncology group study(E2404)[J].Leuk Lymph,2014,55(4):768-772.
[38]Kluin-Nelemans HC,van Marwijk KM,Lugtenburg PJ,et al.Intensified alemtuzumab-CHOP therapy for peripheral T-cell lymphoma[J].Ann Oncol,2011,22(7):1595-1600.
[39]Kim SJ,Yoon DH,Kang HJ,et al.Bortezomib in combination with CHOP as first-line treatment for patients with stageⅢ/Ⅳperipheral T-cell lymphomas:a multicentre,single-arm,phase 2 trial[J].Eur J Cancer,2012,48(17):3223-3231.
[40]Foss FM,Sjak-Shie N,Goy A,et al.A multicenter phaseⅡtrial to determine the safety and efficacy of combination therapy with denileukin diftitox and cyclophosphamide,doxorubicin,vincristine and prednisone in untreated peripheral T-cell lymphoma:the CONCEPT study[J].Leuk Lymph,2013,54(7):1373-1379.
[41]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].J Clin Oncol,2013,31(16):1970-1976.
[42]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].J Clin Oncol,2011,29(9):1182-1189.
[43]Piekarz RL,Frye R,Prince HM,et al.PhaseⅡtrial of romidepsin in patients with peripheral T-cell lymphoma[J].Blood,2011,117(22):5827-5834.
[44]O'Connor OA,Horwitz S,Masszi T,et al.Belinostat in patients with relapsed or refractory peripheral T-cell lymphoma:results of the pivotal phaseⅡBELIEF(CLN-19)Study[J].J Clin Oncol,2015,33(23):2492-2499.
[45]Shi Y,Jia B,Xu W,et al.Chidamide in relapsed or refractory peripheral T cell lymphoma:a multicenter real-world study in China[J].J Hematol Oncol,2017,10(1):69.
[46]D'Amore F,Radford J,Relander T,et al.PhaseⅡtrial of zanolimumab(Hu Max-CD4)in relapsed or refractory non-cutaneous peripheral T cell lymphoma[J].Br J Haematol,2010,150(5):565-573.
[47]Dang NH,Pro B,Hagemeister FB,et al.PhaseⅡtrial of denileukin diftitox for relapsed/refractory T-cell non-Hodgkin lymphoma[J].Br J Haematol,2007,136(3):439-447.
[48]Cerchietti L,Melnick A.Targeting BCL6 in diffuse large B-cell lymphoma:what does this mean for the future treatment[J]?Exp Rev Hematol,2013,6(4):343-345.
[49]Dupont T,Yang SN,Patel J,et al.Selective targeting of BCL6 induces oncogene addiction switching to BCL2 in B-cell lymphoma[J].Oncotarget,2016,7(3):3520-3532.
[50]Platt AM,Gibson VB,Patakas A,et al.Abatacept limits breach of selftolerance in a murine model of arthritis via effects on the generation of T follicular helper cells[J].J Immunol,2010,185(3):1558-1567.
[51]Yang Q,Modi P,Newcomb T,et al.Idelalisib:first-in-class PI3K delta inhibitor for the treatment of chronic lymphocytic leukemia,small lymphocytic leukemia,and follicular lymphoma[J].Clin Cancer Res,2015,21(7):1537-1542.
[52]Chavele KM,Merry E,Ehrenstein MR.Cutting edge:circulating plasmablasts induce the differentiation of human T follicular helper cells via IL-6 production[J].J Immunol,2015,194(6):2482-2485.
[53]Hong D,Kurzrock R,Kim Y,et al.AZD9150,a next-generation antisense oligonucleotide inhibitor of STAT3 with early evidence of clinical activity in lymphoma and lung cancer[J].Sci Transl Med,2015,7(314):185-314.
[54]Klimatcheva E,Pandina T,Reilly C,et al.CXCL13 antibody for the treatment of autoimmune disorders[J].BMC Immunol,2015,16(1):6.
[55]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[J].Hematol Oncol,2017,35(4):864.
[56]Cheminant M,Bruneau J,Kosmider O,et al.Efficacy of 5-azacytidine in a TET2 mutated angioimmunoblastic T cell lymphoma[J].Br J Haematol,2015,168(6):913-916.
[57]Bejar R,Lord A,Stevenson K,et al.TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients[J].Blood,2014,124(17):2705-2712.
[58]Stein EM,Di Nardo CD,Pollyea DA,et al.Enasidenib in mutant IDH2relapsed or refractory acute myeloid leukemia[J].Blood,2017,130(6):722-731.