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Review

Structural genomic alterations in primary mediastinal large B-cell lymphoma

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Pages 2239-2250 | Received 28 Oct 2014, Accepted 02 Nov 2014, Published online: 21 Jan 2015

References

  • Miller JB, Variakojis D, Bitran JD, et al. Diffuse histiocytic lymphoma with sclerosis: a clinicopathologic entity frequently causing superior venacaval obstruction. Cancer 1981;47:748–756.
  • Rosenwald A, Wright G, Leroy K, et al. Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. J Exp Med 2003;198:851–862.
  • Savage KJ, Monti S, Kutok JL, et al. The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma. Blood 2003;102:3871–3879.
  • Swerdlow SH, Campo E, Harris NL, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon: IARC Press; 2008.
  • Steidl C, Gascoyne RD. The molecular pathogenesis of primary mediastinal large B-cell lymphoma. Blood 2011;118:2659–2669.
  • Gunawardana J, Chan FC, Telenius A, et al. Recurrent somatic mutations of PTPN1 in primary mediastinal B cell lymphoma and Hodgkin lymphoma. Nat Genet 2014;46:329–335.
  • Steidl C, Shah SP, Woolcock BW, et al. MHC class II transactivator CIITA is a recurrent gene fusion partner in lymphoid cancers. Nature 2011;471:377–381.
  • Twa DD, Chan FC, Ben-Neriah S, et al. Genomic rearrangements involving programmed death ligands are recurrent in primary mediastinal large B-cell lymphoma. Blood 2014;123:2062–2065.
  • Liu Y, Razak FR, Terpstra M, et al. The mutational landscape of Hodgkin lymphoma cell lines determined by whole exome sequencing. Leukemia 2014;28:2248–2251.
  • Eberle FC, Salaverria I, Steidl C, et al. Gray zone lymphoma: chromosomal aberrations with immunophenotypic and clinical correlations. Mod Pathol 2011;24:1586–1597.
  • Martin-Subero JI, Gesk S, Harder L, et al. Recurrent involvement of the REL and BCL11A loci in classical Hodgkin lymphoma. Blood 2002;99:1474–1477.
  • Martin-Subero JI, Klapper W, Sotnikova A, et al. Chromosomal breakpoints affecting immunoglobulin loci are recurrent in Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma. Cancer Res 2006;66:10332–10338.
  • Meier C, Hoeller S, Bourgau C, et al. Recurrent numerical aberrations of JAK2 and deregulation of the JAK2-STAT cascade in lymphomas. Mod Pathol 2009;22:476–487.
  • Oschlies I, Burkhardt B, Salaverria I, et al. Clinical, pathological and genetic features of primary mediastinal large B-cell lymphomas and mediastinal gray zone lymphomas in children. Haematologica 2011;96:262–268.
  • Van Roosbroeck K, Cox L, Tousseyn T, et al. JAK2 rearrangements, including the novel SEC31A-JAK2 fusion, are recurrent in classical Hodgkin lymphoma. Blood 2011;117:4056–4064.
  • Weniger MA, Gesk S, Ehrlich S, et al. Gains of REL in primary mediastinal B-cell lymphoma coincide with nuclear accumulation of REL protein. Genes Chromosomes Cancer 2007;46:406–415.
  • Barth TF, Martin-Subero JI, Joos S, et al. Gains of 2p involving the REL locus correlate with nuclear c-Rel protein accumulation in neoplastic cells of classical Hodgkin lymphoma. Blood 2003;101:3681–3686.
  • Ernst T, Score J, Deininger M, et al. Identification of FOXP1 and SNX2 as novel ABL1 fusion partners in acute lymphoblastic leukaemia. Br J Haematol 2011;153:43–46.
  • Hoadley KA, Xue Y, Ling C, et al. Defining the molecular interface that connects the Fanconi anemia protein FANCM to the Bloom syndrome dissolvasome. Proc Natl Acad Sci USA 2012;109:4437–4442.
  • Mottok A, Renne C, Seifert M, et al. Inactivating SOCS1 mutations are caused by aberrant somatic hypermutation and restricted to a subset of B-cell lymphoma entities. Blood 2009;114:4503–4506.
  • Keir ME, Latchman YE, Freeman GJ, et al. Programmed death-1 (PD-1): PD-ligand 1 interactions inhibit TCR-mediated positive selection of thymocytes. J Immunol 2005;175:7372–7379.
  • Latchman Y, Wood CR, Chernova T, et al. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol 2001;2:261–268.
  • Adelaide J, Huang HE, Murati A, et al. A recurrent chromosome translocation breakpoint in breast and pancreatic cancer cell lines targets the neuregulin/NRG1 gene. Genes Chromosomes Cancer 2003;37:333–345.
  • Burmeister T, Molkentin M, Schwartz S, et al. Erroneous class switching and false VDJ recombination: molecular dissection of t(8;14)/MYC-IGH translocations in Burkitt-type lymphoblastic leukemia/B-cell lymphoma. Mol Oncol 2013;7:850–858.
  • Roy AL, Sen R, Roeder RG. Enhancer-promoter communication and transcriptional regulation of Igh. Trends Immunol 2011;32: 532–539.
  • Gong AY, Zhou R, Hu G, et al. MicroRNA-513 regulates B7-H1 translation and is involved in IFN-gamma-induced B7-H1 expression in cholangiocytes. J Immunol 2009;182:1325–1333.
  • Rossille D, Gressier M, Damotte D, et al. High level of soluble programmed cell death ligand 1 in blood impacts overall survival in aggressive diffuse large B-cell lymphoma: results from a French multicenter clinical trial. Leukemia 2014 Apr 15. [Epub ahead of print]
  • Bea S, Zettl A, Wright G, et al. Diffuse large B-cell lymphoma subgroups have distinct genetic profiles that influence tumor biology and improve gene-expression-based survival prediction. Blood 2005;106:3183–3190.
  • Bentz M, Barth TF, Bruderlein S, et al. Gain of chromosome arm 9p is characteristic of primary mediastinal B-cell lymphoma (MBL): comprehensive molecular cytogenetic analysis and presentation of a novel MBL cell line. Genes Chromosomes Cancer 2001;30:393–401.
  • Dunphy CH, O’Malley DP, Cheng L, et al. Primary mediastinal B-cell lymphoma: detection of BCL2 gene rearrangements by PCR analysis and FISH. J Hematop 2008;1:77–84.
  • Green MR, Monti S, Rodig SJ, et al. Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma. Blood 2010;116: 3268–3277.
  • Joos S, Otano-Joos MI, Ziegler S, et al. Primary mediastinal (thymic) B-cell lymphoma is characterized by gains of chromosomal material including 9p and amplification of the REL gene. Blood 1996;87:1571–1578.
  • Kimm LR, de Leeuw RJ, Savage KJ, et al. Frequent occurrence of deletions in primary mediastinal B-cell lymphoma. Genes Chromosomes Cancer 2007;46:1090–1097.
  • Lenz G, Wright GW, Emre NC, et al. Molecular subtypes of diffuse large B-cell lymphoma arise by distinct genetic pathways. Proc Natl Acad Sci USA 2008;105:13520–13525.
  • Malpeli G, Barbi S, Moore PS, et al. Primary mediastinal B-cell lymphoma: hypermutation of the BCL6 gene targets motifs different from those in diffuse large B-cell and follicular lymphomas. Haematologica 2004;89:1091–1099.
  • Melzner I, Bucur AJ, Bruderlein S, et al. Biallelic mutation of SOCS-1 impairs JAK2 degradation and sustains phospho-JAK2 action in the MedB-1 mediastinal lymphoma line. Blood 2005;105:2535–2542.
  • Melzner I, Weniger MA, Menz CK, et al. Absence of the JAK2 V617F activating mutation in classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma. Leukemia 2006;20:157–158.
  • Nagel PD, Feld FM, Weissinger SE, et al. Absence of BRAF and KRAS hotspot mutations in primary mediastinal B-cell lymphoma. Leuk Lymphoma 2014;55:2389–2390.
  • Palanisamy N, Abou-Elella AA, Chaganti SR, et al. Similar patterns of genomic alterations characterize primary mediastinal large-B-cell lymphoma and diffuse large-B-cell lymphoma. Genes Chromosomes Cancer 2002;33:114–122.
  • Rigaud G, Moore PS, Taruscio D, et al. Alteration of chromosome arm 6p is characteristic of primary mediastinal B-cell lymphoma, as identified by genome-wide allelotyping. Genes Chromosomes Cancer 2001;31:191–195.
  • Ritz O, Guiter C, Castellano F, et al. Recurrent mutations of the STAT6 DNA binding domain in primary mediastinal B-cell lymphoma. Blood 2009;114:1236–1242.
  • Rui L, Emre NC, Kruhlak MJ, et al. Cooperative epigenetic modulation by cancer amplicon genes. Cancer Cell 2010;18:590–605.
  • Scarpa A, Moore PS, Rigaud G, et al. Molecular features of primary mediastinal B-cell lymphoma: involvement of p16INK4A, p53 and c-myc. Br J Haematol 1999;107:106–113.
  • Schmitz R, Hansmann ML, Bohle V, et al. TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma. J Exp Med 2009;206:981–989.
  • Scholl V, Stefanoff CG, Hassan R, et al. Mutations within the 5’ region of FAS/CD95 gene in nodal diffuse large B-cell lymphoma. Leuk Lymphoma 2007;48:957–963.
  • Takahashi H, Feuerhake F, Monti S, et la.Lack of IKBA coding region mutations in primary mediastinal large B-cell lymphoma and the host response subtype of diffuse large B-cell lymphoma. Blood 2006;107:844–845.
  • Tsang P, Cesarman E, Chadburn A, et al. Molecular characterization of primary mediastinal B cell lymphoma. Am J Pathol 1996;148: 2017–2025.
  • Weniger MA, Pulford K, Gesk S, et al. Gains of the proto-oncogene BCL11A and nuclear accumulation of BCL11A(XL) protein are frequent in primary mediastinal B-cell lymphoma. Leukemia 2006; 20:1880–1882.
  • Wessendorf S, Barth TF, Viardot A, et al. Further delineation of chromosomal consensus regions in primary mediastinal B-cell lymphomas: an analysis of 37 tumor samples using high-resolution genomic profiling (array-CGH). Leukemia 2007;21:2463–2469.
  • Roberts RA, Wright G, Rosenwald AR, et al. Loss of major histocompatibility class II gene and protein expression in primary mediastinal large B-cell lymphoma is highly coordinated and related to poor patient survival. Blood 2006;108:311–318.
  • Abou-Elella AA, Weisenburger DD, Vose JM, et al. Primary mediastinal large B-cell lymphoma: a clinicopathologic study of 43 patients from the Nebraska Lymphoma Study Group. J Clin Oncol 1999;17:784–790.
  • Cazals-Hatem D, Lepage E, Brice P, et al. Primary mediastinal large B-cell lymphoma. A clinicopathologic study of 141 cases compared with 916 nonmediastinal large B-cell lymphomas, a GELA (“Groupe d’Etude des Lymphomes de l’Adulte”) study. Am J Surg Pathol 1996;20:877–888.
  • al-Sharabati M, Chittal S, Duga-Neulat I, et al. Primary anterior mediastinal B-cell lymphoma. A clinicopathologic and immunohistochemical study of 16 cases. Cancer 1991;67:2579–2587.
  • Calaminici M, Piper K, Lee AM, et al. CD23 expression in mediastinal large B-cell lymphomas. Histopathology 2004;45:619–624.
  • Copie-Bergman C, Plonquet A, Alonso MA, et al. MAL expression in lymphoid cells: further evidence for MAL as a distinct molecular marker of primary mediastinal large B-cell lymphomas. Mod Pathol 2002;15:1172–1180.
  • Dorfman DM, Shahsafaei A, Alonso MA. Utility of CD200 immunostaining in the diagnosis of primary mediastinal large B cell lymphoma: comparison with MAL, CD23, and other markers. Mod Pathol 2012;25:1637–1643.
  • Hofmann WJ, Momburg F, Moller P. Thymic medullary cells expressing B lymphocyte antigens. Hum Pathol 1988;19:1280–1287.
  • Isaacson PG, Norton AJ, Addis BJ. The human thymus contains a novel population of B lymphocytes. Lancet 1987;2:1488–1491.
  • Lazzarino M, Orlandi E, Paulli M, et al. Primary mediastinal B-cell lymphoma with sclerosis: an aggressive tumor with distinctive clinical and pathologic features. J Clin Oncol 1993;11:2306–2313.
  • Moller P, Lammler B, Herrmann B, et al. The primary mediastinal clear cell lymphoma of B-cell type has variable defects in MHC antigen expression. Immunology 1986;59:411–417.
  • Pileri SA, Gaidano G, Zinzani PL, et al. Primary mediastinal B-cell lymphoma: high frequency of BCL-6 mutations and consistent expression of the transcription factors OCT-2, BOB.1, and PU.1 in the absence of immunoglobulins. Am J Pathol 2003;162:243–253.
  • Salama ME, Rajan Mariappan M, Inamdar K, et al. The value of CD23 expression as an additional marker in distinguishing mediastinal (thymic) large B-cell lymphoma from Hodgkin lymphoma. Int J Surg Pathol 2010;18:121–128.
  • Spencer J, Choy M, Hussell T, et al. Properties of human thymic B cells. Immunology 1992;75:596–600.
  • Yamamoto W, Nakamura N, Tomita N, et al. Clinicopathological analysis of mediastinal large B-cell lymphoma and classical Hodgkin lymphoma of the mediastinum. Leuk Lymphoma 2013;54:967–972.
  • Csernus B, Timar B, Fulop Z, et al. Mutational analysis of IgVH and BCL-6 genes suggests thymic B-cells origin of mediastinal (thymic) B-cell lymphoma. Leuk Lymphoma 2004;45:2105–2110.
  • de Leval L, Ferry JA, Falini B, et al. Expression of bcl-6 and CD10 in primary mediastinal large B-cell lymphoma: evidence for derivation from germinal center B cells? Am J Surg Pathol 2001;25:1277–1282.
  • De Mello CA, De Andrade VP, De Lima VC, et al. Prognostic impact of MUM1 expression by immunohistochemistry on primary mediastinal large B-cell lymphoma. Leuk Lymphoma 2011;52: 1495–1503.
  • Flores KG, Li J, Hale LP. B cells in epithelial and perivascular compartments of human adult thymus. Hum Pathol 2001;32:926–934.
  • Leithauser F, Bauerle M, Huynh MQ, et al. Isotype-switched immunoglobulin genes with a high load of somatic hypermutation and lack of ongoing mutational activity are prevalent in mediastinal B-cell lymphoma. Blood 2001;98:2762–2770.
  • Marafioti T, Jones M, Facchetti F, et al. Phenotype and genotype of interfollicular large B cells, a subpopulation of lymphocytes often with dendritic morphology. Blood 2003;102:2868–2876.
  • Rossi D, Cerri M, Capello D, et al. Aberrant somatic hypermutation in primary mediastinal large B-cell lymphoma. Leukemia 2005;19: 2363–2366.
  • Akashi K, Richie LI, Miyamoto T, et al. B lymphopoiesis in the thymus. J Immunol 2000;164:5221–5226.
  • Moldenhauer G, Popov SW, Wotschke B, et al. AID expression identifies interfollicular large B cells as putative precursors of mature B-cell malignancies. Blood 2006;107:2470–2473.
  • Mori S, Inaba M, Sugihara A, et al. Presence of B cell progenitors in the thymus. J Immunol 1997;158:4193–4199.
  • Perera J, Meng L, Meng F, et al. Autoreactive thymic B cells are efficient antigen-presenting cells of cognate self-antigens for T cell negative selection. Proc Natl Acad Sci USA 2013;110:17011–17016.
  • Moller P, Moldenhauer G, Momburg F, et al. Mediastinal lymphoma of clear cell type is a tumor corresponding to terminal steps of B cell differentiation. Blood 1987;69:1087–1095.
  • Feuerhake F, Kutok JL, Monti S, et al. NFkappaB activity, function, and target-gene signatures in primary mediastinal large B-cell lymphoma and diffuse large B-cell lymphoma subtypes. Blood 2005;106:1392–1399.
  • Calvo KR, Traverse-Glehen A, Pittaluga S, et al. Molecular profiling provides evidence of primary mediastinal large B-cell lymphoma as a distinct entity related to classic Hodgkin lymphoma: implications for mediastinal gray zone lymphomas as an intermediate form of B-cell lymphoma. Adv Anat Pathol 2004;11:227–238.
  • Eberle FC, Rodriguez-Canales J, Wei L, et al. Methylation profiling of mediastinal gray zone lymphoma reveals a distinctive signature with elements shared by classical Hodgkin's lymphoma and primary mediastinal large B-cell lymphoma. Haematologica 2011;96:558–566.
  • Han L, Masani S, Yu K. Overlapping activation-induced cytidine deaminase hotspot motifs in Ig class-switch recombination. Proc Natl Acad Sci USA 2011;108:11584–11589.
  • Martin A, Bardwell PD, Woo CJ, et al. Activation-induced cytidine deaminase turns on somatic hypermutation in hybridomas. Nature 2002;415:802–806.
  • Rogozin IB, Diaz M. Cutting edge: DGYW/WRCH is a better predictor of mutability at G:C bases in Ig hypermutation than the widely accepted RGYW/WRCY motif and probably reflects a two-step activation-induced cytidine deaminase-triggered process. J Immunol 2004;172:3382–3384.
  • Chiarle R, Zhang Y, Frock RL, et al. Genome-wide translocation sequencing reveals mechanisms of chromosome breaks and rearrangements in B cells. Cell 2011;147:107–119.
  • Klein IA, Resch W, Jankovic M, et al. Translocation-capture sequencing reveals the extent and nature of chromosomal rearrangements in B lymphocytes. Cell 2011;147:95–106.
  • Steidl C, Woolcock B, Rogic S, et al. Inactivating gene alterations of MHC class II transactivator CIITA are recurrent in primary mediastinal B cell lymphoma and Hodgkin lymphoma. Blood 2011;118(Suppl. 1): Abstract 437.
  • Wang CL, Harper RA, Wabl M. Genome-wide somatic hypermutation. Proc Natl Acad Sci USA 2004;101:7352–7356.
  • Greisman HA, Lu Z, Tsai AG, et al. IgH partner breakpoint sequences provide evidence that AID initiates t(11;14) and t(8;14) chromosomal breaks in mantle cell and Burkitt lymphomas. Blood 2012;120:2864–2867.
  • Ramiro AR, Jankovic M, Eisenreich T, et al. AID is required for c-myc/IgH chromosome translocations in vivo. Cell 2004;118:431–438.
  • Bodor C, Bognar A, Reiniger L, et al. Aberrant somatic hypermutation and expression of activation-induced cytidine deaminase mRNA in mediastinal large B-cell lymphoma. Br J Haematol 2005;129:373–376.
  • Okazaki IM, Hiai H, Kakazu N, et al. Constitutive expression of AID leads to tumorigenesis. J Exp Med 2003;197:1173–1181.
  • Barlow JH, Faryabi RB, Callen E, et al. Identification of early replicating fragile sites that contribute to genome instability. Cell 2013;152:620–632.
  • Jiang Y, Soong TD, Wang L, et al. Genome-wide detection of genes targeted by non-Ig somatic hypermutation in lymphoma. PLoS One 2012;7:e40332.
  • Khodabakhshi AH, Morin RD, Fejes AP, et al. Recurrent targets of aberrant somatic hypermutation in lymphoma. Oncotarget 2012; 3:1308–1319.
  • Klein U, Dalla-Favera R. Germinal centres: role in B-cell physiology and malignancy. Nat Rev Immunol 2008;8:22–33.
  • Vakiani E, Basso K, Klein U, et al. Genetic and phenotypic analysis of B-cell post-transplant lymphoproliferative disorders provides insights into disease biology. Hematol Oncol 2008;26:199–211.
  • Tsai AG, Lu H, Raghavan SC, et al. Human chromosomal translocations at CpG sites and a theoretical basis for their lineage and stage specificity. Cell 2008;135:1130–1142.
  • Wang JH, Gostissa M, Yan CT, et al. Mechanisms promoting translocations in editing and switching peripheral B cells. Nature 2009;460:231–236.
  • Albertson DG. Gene amplification in cancer. Trends Genet 2006;22:447–455.
  • Wright SM, Woo YH, Alley TL, et al. Complex oncogenic translocations with gene amplification are initiated by specific DNA breaks in lymphocytes. Cancer Res 2009;69:4454–4460.
  • Bester AC, Roniger M, Oren YS, et al. Nucleotide deficiency promotes genomic instability in early stages of cancer development. Cell 2011;145:435–446.
  • Jones RM, Mortusewicz O, Afzal I, et al. Increased replication initiation and conflicts with transcription underlie Cyclin E-induced replication stress. Oncogene 2013;32:3744–3753.
  • Ozeri-Galai E, Bester AC, Kerem B. The complex basis underlying common fragile site instability in cancer. Trends Genet 2012;28:295–302.
  • Ozeri-Galai E, Lebofsky R, Rahat A, et al. Failure of origin activation in response to fork stalling leads to chromosomal instability at fragile sites. Mol Cell 2011;43:122–131.
  • Toledo F, Smith KA, Buttin G, et al. The evolution of the amplified adenylate deaminase 2 domains in Chinese hamster cells suggests the sequential operation of different mechanisms of DNA amplification. Mutat Res 1992;276:261–273.
  • Scott DW, Gascoyne RD. The tumour microenvironment in B cell lymphomas. Nat Rev Cancer 2014;14:517–534.
  • Armand P, Nagler A, Weller EA, et al. Disabling immune tolerance by programmed death-1 blockade with pidilizumab after autologous hematopoietic stem-cell transplantation for diffuse large B-cell lymphoma: results of an international phase II trial. J Clin Oncol 2013;31:4199–4206.
  • Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 2012;366:2455–2465.
  • Cervantes F, Vannucchi AM, Kiladjian JJ, et al. Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis. Blood 2013;122:4047–4053.
  • Eghtedar A, Verstovsek S, Estrov Z, et al. Phase 2 study of the JAK kinase inhibitor ruxolitinib in patients with refractory leukemias, including postmyeloproliferative neoplasm acute myeloid leukemia. Blood 2012;119:4614–4618.
  • Hamid O, Robert C, Daud A, et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med 2013;369:134–144.
  • Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med 2012;366:787–798.
  • Mesa RA, Gotlib J, Gupta V, et al. Effect of ruxolitinib therapy on myelofibrosis-related symptoms and other patient-reported outcomes in COMFORT-I: a randomized, double-blind, placebo-controlled trial. J Clin Oncol 2013;31:1285–1292.
  • Pardanani A, Gotlib JR, Jamieson C, et al. Safety and efficacy of TG101348, a selective JAK2 inhibitor, in myelofibrosis. J Clin Oncol 2011;29:789–796.
  • Santos FP, Kantarjian HM, Jain N, et al. Phase 2 study of CEP-701, an orally available JAK2 inhibitor, in patients with primary or post-polycythemia vera/essential thrombocythemia myelofibrosis. Blood 2010;115:1131–1136.
  • Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012;366:2443–2454.
  • Topalian SL, Sznol M, McDermott DF, et al. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol 2014;32: 1020–1030.
  • Verstovsek S, Kantarjian HM, Estrov Z, et al. Long-term outcomes of 107 patients with myelofibrosis receiving JAK1/JAK2 inhibitor ruxolitinib: survival advantage in comparison to matched historical controls. Blood 2012;120:1202–1209.
  • Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med 2012;366:799–807.
  • Weber JS, Kudchadkar RR, Yu B, et al. Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma. J Clin Oncol 2013;31:4311–4318.
  • Westin JR, Chu F, Zhang M, et al. Safety and activity of PD1 blockade by pidilizumab in combination with rituximab in patients with relapsed follicular lymphoma: a single group, open-label, phase 2 trial. Lancet Oncol 2014;15:69–77.
  • Wolchok JD, Kluger H, Callahan MK, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med 2013;369:122–133.
  • Brahmer JR, Drake CG, Wollner I, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol 2010;28:3167–3175.
  • Levis M, Ravandi F, Wang ES, et al. Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse. Blood 2011;117:3294–3301.
  • Verstovsek S, Mesa RA, Gotlib J, et al. The clinical benefit of ruxolitinib across patient subgroups: analysis of a placebo-controlled, phase III study in patients with myelofibrosis. Br J Haematol 2013;161:508–516.
  • Verstovsek S, Mesa RA, Gotlib J, et al. Efficacy, safety and survival with ruxolitinib in patients with myelofibrosis: results of a median 2-year follow-up of COMFORT-I. Haematologica 2013;98:1865–1871.
  • Mesa RA, Kiladjian JJ, Verstovsek S, et al. Comparison of placebo and best available therapy for the treatment of myelofibrosis in the phase 3 COMFORT studies. Haematologica 2014;99:292–298.
  • Verstovsek S, Kantarjian H, Mesa RA, et al. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med 2010;363:1117–1127.
  • Robert C, Ribas A, Wolchok JD, et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet 2014;384:1109–1117.
  • Verstovsek S, Passamonti F, Rambaldi A, et al. A phase 2 study of ruxolitinib, an oral JAK1 and JAK2 Inhibitor, in patients with advanced polycythemia vera who are refractory or intolerant to hydroxyurea. Cancer 2014;120:513–520.
  • Hexner E, Roboz G, Hoffman R, et al. Open-label study of oral CEP-701 (lestaurtinib) in patients with polycythaemia vera or essential thrombocythaemia with JAK2-V617F mutation. Br J Haematol 2014;164:83–93.
  • Talpaz M, Paquette R, Afrin L, et al. Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts. J Hematol Oncol 2013;6:81.
  • Younes A, Romaguera J, Fanale M, et al. Phase I study of a novel oral Janus kinase 2 inhibitor, SB1518, in patients with relapsed lymphoma: evidence of clinical and biologic activity in multiple lymphoma subtypes. J Clin Oncol 2012;30:4161–4167.
  • Rayner LE, Hui GK, Gor J, et al. The Fab conformations in the solution structure of human IgG4 restricts access to its Fc region: implications for functional activity. J Biol Chem 2014;289:20740–20756.
  • Salfeld JG. Isotype selection in antibody engineering. Nat Biotechnol 2007;25:1369–1372.
  • Gatenby RA, Silva AS, Gillies RJ, et al. Adaptive therapy. Cancer Res 2009;69:4894–4903.
  • Butte MJ, Keir ME, Phamduy TB, et al. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity 2007;27:111–122.
  • Cheng X, Veverka V, Radhakrishnan A, et al. Structure and interactions of the human programmed cell death 1 receptor. J Biol Chem 2013;288:11771–11785.
  • Youngnak P, Kozono Y, Kozono H, et al. Differential binding properties of B7-H1 and B7-DC to programmed death-1. Biochem Biophys Res Commun 2003;307:672–677.
  • Hao Y, Chapuy B, Monti S, et al. Selective JAK2 inhibition specifically decreases Hodgkin lymphoma and mediastinal large B-cell lymphoma growth in vitro and in vivo. Clin Cancer Res 2014;20:2674–2683.

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