567
Views
8
CrossRef citations to date
0
Altmetric
Review Article

Targeting oncogenic and epigenetic survival pathways in lymphoma

&
Pages 2365-2376 | Received 15 Dec 2012, Accepted 22 Feb 2013, Published online: 22 Apr 2013

References

  • 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;328:1002–1006.
  • Hibbs ML, Tarlinton DM, Armes J, et al. Multiple defects in the immune system of Lyn-deficient mice, culminating in autoimmune disease. Cell 1995;83:301–311.
  • Turner M, Mee PJ, Costello PS, et al. Perinatal lethality and blocked B-cell development in mice lacking the tyrosine kinase Syk. Nature 1995;378:298–302.
  • Cheng AM, Rowley B, Pao W, et al. Syk tyrosine kinase required for mouse viability and B-cell development. Nature 1995;378:303–306.
  • Abtahian F, Guerriero A, Sebzda E, et al. Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk. Science 2003;299:247–251.
  • Rolli V, Gallwitz M, Wossning T, et al. Amplification of B cell antigen receptor signaling by a Syk/ITAM positive feedback loop. Mol Cell 2002;10:1057–1069.
  • Lam KP, Kuhn R, Rajewsky K, In vivo ablation of surface immunoglobulin on mature B cells by inducible gene targeting results in rapid cell death. Cell 1997;90:1073–1083.
  • Kraus M, Alimzhanov MB, Rajewsky N, et al. Survival of resting mature B lymphocytes depends on BCR signaling via the Igalpha/beta heterodimer. Cell 2004;117:787–800.
  • Davis RE, Ngo VN, Lenz G, et al. Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature 2010;463:88–92.
  • Chen L, Juszczynski P, Takeyama K, et al. Protein tyrosine phosphatase receptor-type O truncated (PTPROt) regulates SYK phosphorylation, proximal B-cell-receptor signaling, and cellular proliferation. Blood 2006;108:3428–3433.
  • Chen LF, Monti S, Juszczynski P, et al. SYK-dependent tonic B-cell receptor signaling is a rational treatment target in diffuse large B-cell lymphoma. Blood 2008;111:2230–2237.
  • Braselmann S, Taylor V, Zhao H, et al. R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation. J Pharmacol Exp Ther 2006;319:998–1008.
  • Friedberg JW, Sharman J, Sweetenham J, et al. Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia. Blood 2010;115:2578–2585.
  • Honigberg LA, Smith AM, Sirisawad M, et al. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Proc Natl Acad Sci USA 2010;107:13075–13080.
  • Herman SEM, Gordon AL, Hertlein E, et al. Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765. Blood 2011;117:6287–6296.
  • Advani RH, Buggy JJ, Sharman JP, et al. Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. J Clin Oncol 2013;31:88–94.
  • Wang LH, Martin P, Blum KA, et al. The Bruton's tyrosine kinase inhibitor PCI-32765 is highly active as single-agent therapy in previously-treated mantle cell lymphoma (MCL): preliminary results of a phase II trial. Blood 2011;118:203–204.
  • Byrd JC, Furman RR, Coutre SE, et al. The Bruton's tyrosine kinase (BTK) inhibitor PCI-32765 (P) in treatment-naive (TN) chronic lymphocytic leukemia (CLL) patients (pts): interim results of a phase Ib/II study. J Clin Oncol 2012;30(Suppl.): Abstract 6507.
  • Foster FM, Traer CJ, Abraham SM, et al. The phosphoinositide (PI) 3-kinase family. J Cell Sci 2003;116:3037–3040.
  • Wurmser AE, Gary JD, Emr SD, Phosphoinositide 3-kinases and their FYVE domain-containing effectors as regulators of vacuolar/lysosomal membrane trafficking pathways. J Biol Chem 1999;274:9129–9132.
  • Volinia S, Dhand R, Vanhaesebroeck B, et al. A human phosphatidylinositol 3-kinase complex related to the yeast Vps34p-Vps15p protein sorting system. EMBO J 1995;14:3339–3348.
  • Zhou XA, Takatoh J, Wang F. The mammalian class 3 PI3K (PIK3C3) is required for early embryogenesis and cell proliferation. PLoS One 2011;6:e16358.
  • Katso R, Okkenhaug K, Ahmadi K, et al. Cellular function of phosphoinositide 3-kinases: implications for development, homeostasis, and cancer. Annu Rev Cell Dev Biol 2001;17:615–675.
  • Domin J, Harper L, Aubyn D, et al. The class II phosphoinositide 3-kinase PI3K-C2 beta regulates cell migration by a PtdIns(3)P dependent mechanism. J Cell Physiol 2005;205:452–462.
  • Samuels Y, Wang Z, Bardelli A, et al. High frequency of mutations of the PIK3CA gene in human cancers. Science 2004;304:554.
  • Bi L, Okabe I, Bernard DJ, et al. Proliferative defect and embryonic lethality in mice homozygous for a deletion in the p110alpha subunit of phosphoinositide 3-kinase. J Biol Chem 1999;274:10963–10968.
  • Bi L, Okabe I, Bernard DJ, et al. Early embryonic lethality in mice deficient in the p110beta catalytic subunit of PI 3-kinase Mamm. Genome 2002;13:169–172.
  • Jou ST, Carpino N, Takahashi Y, et al. Essential, nonredundant role for the phosphoinositide 3-kinase p110delta in signaling by the B-cell receptor complex. Mol Cell Biol 2002;22:8580–8591.
  • Vanhaesebroeck B, Ali K, Bilancio A, et al. Signalling by PI3K isoforms: insights from gene-targeted mice. Trends Biochem Sci 2005;30:194–204.
  • Sasaki T, Irie-Sasaki J, Jones RG, et al. Function of PI3Kgamma in thymocyte development, T cell activation, and neutrophil migration. Science 2000;287:1040–1046.
  • Cai SL, Tee AR, Short JD, et al. Activity of TSC2 is inhibited by AKT-mediated phosphorylation and membrane partitioning. J Cell Biol 2006;173:279–289.
  • Gingras AC, Kennedy SG, O’Leary MA, et al. 4E-BP1, a repressor of mRNA translation, is phosphorylated and inactivated by the Akt(PKB) signaling pathway. Genes Dev 1998;12:502–513.
  • Reif K, Okkenhaug K, Sasaki T, et al. Cutting edge: differential roles for phosphoinositide 3-kinases, p110gamma and p110delta, in lymphocyte chemotaxis and homing. J Immunol 2004;173:2236–2240.
  • Furman RR, Byrd JC, Flinn I, et al. Interim results from a phase I study of CAL-101, a selective oral inhibitor of phosphatidylinositol 3-kinase p110δ isoform, in patients with relapsed or refractory hematologic malignancies. J Clin Oncol 2010;28(15 Suppl.): Abstract 3032.
  • Coutre S, Byrd JC, Furman RR, et al. Phase I study of CAL-101, an isoform-selective inhibitor of phosphatidylinositol 3-kinase P110d, in patients with previously treated chronic lymphocytic leukemia. J Clin Oncol 2011;29(Suppl.): Abstract 6631.
  • Leonard J, Schreeder M, Coutre S, et al. A phase 1 study of Cal-101, an isoform-selective inhibitor of phosphatidylinositol 3-kinase P110d, in combination with anti-CD20 monoclonal antibody therapy and/or bendamustine in patients with previously treated B-cell malignancies. Ann Oncol 2011;22:137.
  • Webb LM, Vigorito E, Wymann MP, et al. Cutting edge: T cell development requires the combined activities of the p110gamma and p110delta catalytic isoforms of phosphatidylinositol 3-kinase. J Immunol 2005;175:2783–2787.
  • Swat W, Montgrain V, Doggett TA, et al. Essential role of PI3Kdelta and PI3Kgamma in thymocyte survival. Blood 2006;107:2415–2422.
  • Buglio D, Lemoine M, Estrella J, et al. The allosteric AKT inhibitor MK-2206 demonstrates potent antiproliferative activity in lymphoma cells and synergizes with the HDAC inhibitor vorinostat. Blood 2011;118:1592–1593.
  • Ansell SM, Inwards DJ, Rowland KM Jr, et al. Low-dose, single-agent temsirolimus for relapsed mantle cell lymphoma: a phase 2 trial in the North Central Cancer Treatment Group. Cancer 2008;113: 508–514.
  • Smith SM, van Besien K, Karrison T, et al. Temsirolimus has activity in non-mantle cell non-Hodgkin's lymphoma subtypes: The University of Chicago phase II consortium. J Clin Oncol 2010;28:4740–4746.
  • Hess G, Herbrecht R, Romaguera J, et al. Phase III study to evaluate temsirolimus compared with investigator's choice therapy for the treatment of relapsed or refractory mantle cell lymphoma. J Clin Oncol 2009;27:3822–3829.
  • Ansell SM, Tang H, Kurtin PJ, et al. Temsirolimus and rituximab in patients with relapsed or refractory mantle cell lymphoma: a phase 2 study. Lancet Oncol 2011;12:361–368.
  • Witzig E, Habermann T, Reeder C, et al. A phase II trial of the oral mTOR inhibitor everolimus in relapsed non-Hodgkin lymphoma (NHL) and Hodgkin disease (HD). Presented at 14th Congress of the European Hematology Association, Berlin, Germany, 2009; Abstract 1081.
  • Witzig TE, Reeder CB, LaPlant BR, et al. A phase II trial of the oral mTOR inhibitor everolimus in relapsed aggressive lymphoma. Leukemia 2011;25:341–347.
  • Johnston PB, Inwards DJ, Colgan JP, et al. A phase II trial of the oral mTOR inhibitor everolimus in relapsed Hodgkin lymphoma. Am J Hematol 2010;85:320–324.
  • Zent CS, LaPlant BR, Johnston PB, et al. The treatment of recurrent/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) with everolimus results in clinical responses and mobilization of CLL cells into the circulation. Cancer 2010;116: 2201–2207.
  • Johnston P, Pinter-Brown L, Rogerio J, et al. Everolimus (EVE) for relapsed/refractory classical Hodgkin lymphoma (cHL): open-label, single-arm, phase II study. J Clin Oncol 2012;30(Suppl.): Abstract 8028.
  • Apsel B, Blair JA, Gonzalez B, et al. Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases. Nat Chem Biol 2008;4:691–699.
  • Zhang YJ, Duan YW, Zheng XFS. Targeting the mTOR kinase domain: the second generation of mTOR inhibitors. Drug Discov Today 2011;16:325–331.
  • Chresta CM, Davies BR, Hickson I, et al. AZD8055 is a potent, selective, and orally bioavailable ATP-competitive mammalian target of rapamycin kinase inhibitor with in vitro and in vivo antitumor activity. Cancer Res 2010;70:288–298.
  • Yu K, Shi C, Toral-Barza L, et al. Beyond rapalog therapy: preclinical pharmacology and antitumor activity of WYE-125132, an ATP-competitive and specific inhibitor of mTORC1 and mTORC2. Cancer Res 2010;70:621–631.
  • Yu K, Toral-Barza L, Shi C, et al. Biochemical, cellular, and in vivo activity of novel ATP-competitive and selective inhibitors of the mammalian target of rapamycin. Cancer Res 2009;69:6232–6240.
  • Lemoine M, Derenzini E, Buglio D, et al. The pan-deacetylase inhibitor panobinostat induces cell death and synergizes with everolimus in Hodgkin lymphoma cell lines. Blood 2012;119: 4017–4025.
  • Younes A, Copeland A, Fanale M, et al. Safety and efficacy of the novel combination of panobinostat (LBH589) and everolimus (RAD001) in relapsed/refractory Hodgkin and non-Hodgkin lymphoma. Blood 2011;118(Suppl.): Abstract 3718.
  • Ngo VN, Young RM, Schmitz R, et al. Oncogenically active MYD88 mutations in human lymphoma. Nature 2011;470:115–119.
  • Lin SC, Lo YC, Wu H. Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling. Nature 2010;465:885–890.
  • Ding BB, Yu JJ, Yu RY, et al. Constitutively activated STAT3 promotes cell proliferation and survival in the activated B-cell subtype of diffuse large B-cell lymphomas. Blood 2008;111:1515–1523.
  • Lam LT, Wright G, Davis RE, et al. Cooperative signaling through the signal transducer and activator of transcription 3 and nuclear factor-kappa B pathways in subtypes of diffuse large B-cell lymphoma. Blood 2008;111:3701–3713.
  • Derenzini E, Lemoine M, Buglio D, et al. The JAK inhibitor AZD1480 regulates proliferation and immunity in Hodgkin lymphoma. Blood Cancer J 2011;1:e46.
  • 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.
  • Pasqualucci L, Dominguez-Sola D, Chiarenza A, et al. Inactivating mutations of acetyltransferase genes in B-cell lymphoma. Nature 2011;471:189–195.
  • Kirschbaum M, Frankel P, Popplewell L, et al. Phase II study of vorinostat for treatment of relapsed or refractory indolent non-Hodgkin's lymphoma and mantle cell lymphoma. J Clin Oncol 2011;29:1198–1203.
  • Ando K, Ogura M, Suzuki T, et al. A multicenter phase II study of vorinostat in patients (pts) with relapsed or refractory indolent B-cell non-Hodgkin lymphoma (B-NHL) or mantle cell lymphoma (MCL). J Clin Oncol 2012;30(Suppl.): Abstract 8029.
  • Crump M, Coiffier B, Jacobsen ED, et al. Phase II trial of oral vorinostat (suberoylanilide hydroxamic acid) in relapsed diffuse large-B-cell lymphoma. Ann Oncol 2008;19:964–969.
  • Kirschbaum MH, Goldman BH, Zain JM, et al. A phase 2 study of vorinostat for treatment of relapsed or refractory Hodgkin lymphoma: Southwest Oncology Group Study S0517. Leuk Lymphoma 2012;53: 259–262.
  • Younes A, Wedgewood A, McLaughlin P, et al. Treatment of relapsed or refractory lymphoma with the oral isotype-selective histone deacetylase inhibitor MGCD0103: interim results from a phase II study. Blood 2007;110(Suppl. 1): Abstract 2571.
  • Younes A, Oki Y, Bociek RG, et al. Mocetinostat for relapsed classical Hodgkin's lymphoma: an open-label, single-arm, phase 2 trial. Lancet Oncol 2011;12:1222–1228.
  • Younes A, Sureda A, Ben-Yehuda D, et al. Panobinostat in patients with relapsed/refractory Hodgkin's lymphoma after autologous stem-cell transplantation: results of a phase II study. J Clin Oncol 2012;30:2197–2203.
  • Sparmann A, van Lohuizen M. Polycomb silencers control cell fate, development and cancer. Nat Rev Cancer 2006;6:846–856.
  • Jacobs JJL, Scheijen B, Voncken JW, et al. Bmi-1 collaborates with c-Myc in tumorigenesis by inhibiting c-Myc-induced apoptosis via INK4a/ARF. Genes Dev 1999;13:2678–2690.
  • Haupt Y, Alexander WS, Barri G, et al. Novel zinc finger gene implicated as Myc collaborator by retrovirally accelerated lymphomagenesis in E-Mu-Myc transgenic mice. Cell 1991;65: 753–763.
  • Vanlohuizen M, Verbeek S, Scheijen B, et al. Identification of cooperating oncogenes in E-Mu-Myc transgenic mice by provirus tagging. Cell 1991;65:737–752.
  • van Kemenade FJ, Raaphorst FM, Blokzijl T, et al. Coexpression of BMI-1 and EZH2 polycomb-group proteins is associated with cycling cells and degree of malignancy in B-cell non-Hodgkin lymphoma. Blood 2001;97:3896–3901.
  • Velichutina I, Shaknovich R, Geng HM, et al. EZH2-mediated epigenetic silencing in germinal center B cells contributes to proliferation and lymphomagenesis. Blood 2010;116:5247–5255.
  • 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;42:181–185.
  • Ryan RJ, Nitta M, Borger D, et al. EZH2 codon 641 mutations are common in BCL2-rearranged germinal center B cell lymphomas. PLoS One 2011;6:e28585.
  • Yap DB, Chu J, Berg T, et al. Somatic mutations at EZH2 Y641 act dominantly through a mechanism of selectively altered PRC2 catalytic activity, to increase H3K27 trimethylation. Blood 2011;117:2451–2459.
  • Sneeringer CJ, Scott MP, Kuntz KW, et al. Coordinated activities of wild-type plus mutant EZH2 drive tumor-associated hypertrimethylation of lysine 27 on histone H3 (H3K27) in human B-cell lymphomas. Proc Natl Acad Sci USA 2010;107:20980–20985.
  • Majer CR, Jin L, Scott MP, et al. A687V EZH2 is a gain-of-function mutation found in lymphoma patients. FEBS Lett 2012;19:3448–3451.
  • Chen SA, Bohrer LR, Rai AN, et al. Cyclin-dependent kinases regulate epigenetic gene silencing through phosphorylation of EZH2. Nat Cell Biol 2010;12:1108–1114.
  • Tang XH, Milyavsky M, Shats I, et al. Activated p53 suppresses the histone methyltransferase EZH2 gene. Oncogene 2004;23:5759–5769.
  • McCabe MT, Graves AP, Ganji G, et al. Mutation of A677 in histone methyltransferase EZH2 in human B-cell lymphoma promotes hypertrimethylation of histone H3 on lysine 27 (H3K27). Proc Natl Acad Sci USA 2012;109:2989–9294.
  • Fiskus W, Wang YC, Sreekumar A, et al. Combined epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin A and the histone deacetylase inhibitor panobinostat against human AML cells. Blood 2009;114:2733–2743.
  • Xie ZG, Bi CL, Cheong LL, et al. Determinants of sensitivity to DZNep induced apoptosis in multiple myeloma cells. PLoS One, 2011;6:e21583.
  • Miranda TB, Cortez CC, Yoo CB, et al. DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by DNA methylation. Mol Cancer Ther 2009;8:1579–1588.
  • McCabe MT, Ott HM, Ganji G, et al. EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature 2012;492:108–112.
  • Knutson SK, Wigle TJ, Warholic NM, et al. A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells. Nat Chem Biol 2012;8:890–896.
  • Zuber J, Shi JW, Wang E, et al. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature 2011;478: 524–528.
  • Delmore JE, Issa GC, Lemieux ME, et al. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell 2011;146: 903–916.
  • Mertz JA, Conery AR, Bryant BM, et al. Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proc Natl Acad Sci USA 2011;108:16669–16674.

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.