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International Journal of Hematology

Erschienen in:

01.11.2012 | Progress in Hematology

Diffuse large B cell lymphoma: molecular targeted therapy

verfasst von: Mark Roschewski, Kieron Dunleavy, Wyndham H. Wilson

Erschienen in: International Journal of Hematology | Ausgabe 5/2012

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Abstract

Diffuse large B cell lymphoma (DLBCL) is a biologically heterogeneous disease and the most common subtype of B cell non-Hodgkin’s lymphoma in the USA. Even though it is a curable lymphoma in advanced stages, up to 40 % of patients eventually relapse or fail to achieve remission. Improved understanding of the biologic complexity of DLBCL reveals a diverse range of oncogenic driver mutations and signaling pathways that are essential for growth and survival of malignant cells. Since many of these signaling pathways can be targeted by small-molecule inhibitors, the therapy for DLBCL is currently undergoing a paradigm shift away from conventional chemotherapy and toward targeted agents that capitalize on an improved biologic understanding of the subsets with the highest risk of treatment failure. Participation in well-conducted and rationally designed clinical trials will be essential to realize the potential of these targeted agents and realize the goal of improving overall outcomes in the most common B cell lymphoma in the world.

Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA. Cancer J Clin. 2012;62(1):10–29.

DeVita VT, Jr., Canellos GP, Chabner B, Schein P, Hubbard SP, Young RC. Advanced diffuse histiocytic lymphoma, a potentially curable disease. Lancet. 1975;1(7901):248–50.

Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, 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):1002–6.PubMedCrossRef

Pfreundschuh M, Trumper L, Kloess M, Schmits R, Feller AC, Rudolph C, et al. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood. 2004;104(3):626–33.PubMedCrossRef

Wilson WH, Grossbard ML, Pittaluga S, Cole D, Pearson D, Drbohlav N, et al. Dose-adjusted EPOCH chemotherapy for untreated large B cell lymphomas: a pharmacodynamic approach with high efficacy. Blood. 2002;99(8):2685–93.PubMedCrossRef

Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B cell lymphoma. N Engl J Med. 2002;346(4):235–42.PubMedCrossRef

Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S, et al. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d’Etudes des Lymphomes de l’Adulte. Blood. 2010;116(12):2040–5.PubMedCrossRef

Pfreundschuh M, Trumper L, Osterborg A, Pettengell R, Trneny M, Imrie K, et al. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006;7(5):379–91.PubMedCrossRef

Pfreundschuh M, Kuhnt E, Trumper L, Osterborg A, Trneny M, Shepherd L, et al. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011;12(11):1013–22.PubMedCrossRef

10.

Lee L, Crump M, Khor S, Hoch JS, Luo J, Bremner K, et al. Impact of rituximab on treatment outcomes of patients with diffuse large B cell lymphoma: a population-based analysis. Br J Haematol. 2012;158(4):481–8.PubMedCrossRef

11.

Wilson WH, Dunleavy K, Pittaluga S, Hegde U, Grant N, Steinberg SM, et al. Phase II study of dose-adjusted EPOCH and rituximab in untreated diffuse large B cell lymphoma with analysis of germinal center and post-germinal center biomarkers. J Clin Oncol. 2008;26(16):2717–24.PubMedCrossRef

12.

Wilson WH, Jung SH, Porcu P, Hurd D, Johnson J, Martin SE, et al. A Cancer and Leukemia Group B multi-center study of DA-EPOCH-rituximab in untreated diffuse large B cell lymphoma with analysis of outcome by molecular subtype. Haematologica. 2011;97(5):758–65.PubMedCrossRef

13.

Fu K, Weisenburger DD, Choi WWL, Perry KD, Smith LM, Shi X, et al. Addition of rituximab to standard chemotherapy improves the survival of both the germinal center B cell-like and non-germinal center B cell-like subtypes of diffuse large B cell lymphoma. J Clin Oncol. 2008;26(28):4587–94.PubMedCrossRef

14.

A predictive model for aggressive non-Hodgkin’s lymphoma. The International Non-Hodgkin’s Lymphoma Prognostic Factors project. N Engl J Med. 1993;329(14):987–94.

15.

Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, et al. Distinct types of diffuse large B cell lymphoma identified by gene expression profiling. Nature. 2000;403(6769):503–11.

16.

Rosenwald A, Wright G, Chan WC, Connors JM, Campo E, Fisher RI, et al. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B cell lymphoma. N Engl J Med. 2002;346(25):1937–47.PubMedCrossRef

17.

Rosenwald A, Wright G, Leroy K, Yu X, Gaulard P, Gascoyne RD, 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(6):851–62.PubMedCrossRef

18.

Wright G, Tan B, Rosenwald A, Hurt EH, Wiestner A, Staudt LM. A gene expression-based method to diagnose clinically distinct subgroups of diffuse large B cell lymphoma. Proc Natl Acad Sci USA. 2003;100(17):9991–6.PubMedCrossRef

19.

Lenz G, Wright GW, Emre NCT, Kohlhammer H, Dave SS, Davis RE, et al. Molecular subtypes of diffuse large B cell lymphoma arise by distinct genetic pathways. Proc Nat Acad Sci. 2008;105(36):13520–5.PubMedCrossRef

20.

Dunleavy K, Pittaluga S, Shovlin M, Grant N, Grant C, Chen C, et al. Untreated primary mediastinal B cell (PMBL) and mediastinal grey zone (MGZL) lymphomas: comparison of biological features and clinical outcome following DA-EPOCH-R without radiation. Annals Oncol. 2011;22 (supplement 4):(Abstract 150).

21.

Lenz G, Wright G, Dave SS, Xiao W, Powell J, Zhao H, et al. Stromal gene signatures in large-B cell lymphomas. N Engl J Med. 2008;359(22):2313–23.PubMedCrossRef

22.

Davis RE, Brown KD, Siebenlist U, Staudt LM. Constitutive nuclear factor kappaB activity is required for survival of activated B cell-like diffuse large B cell lymphoma cells. J Exp Med. 2001;194(12):1861–74.PubMedCrossRef

23.

Lim KH, Yang Y, Staudt LM. Pathogenetic importance and therapeutic implications of NF-kappaB in lymphoid malignancies. Immunol Rev. 2012;246(1):359–78.PubMedCrossRef

24.

Davis RE, Ngo VN, Lenz G, Tolar P, Young RM, Romesser PB, et al. Chronic active B cell-receptor signalling in diffuse large B cell lymphoma. Nature. 2010;463(7277):88–92.PubMedCrossRef

25.

Lenz G, Davis RE, Ngo VN, Lam L, George TC, Wright GW, et al. Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science. 2008;319(5870):1676–9.PubMedCrossRef

26.

Ngo VN, Young RM, Schmitz R, Jhavar S, Xiao W, Lim KH, et al. Oncogenically active MYD88 mutations in human lymphoma. Nature. 2011;470(7332):115–9.PubMedCrossRef

27.

Ding BB, Yu JJ, Yu RY, Mendez LM, Shaknovich R, Zhang Y, 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(3):1515–23.PubMedCrossRef

28.

Lam LT, Wright G, Davis RE, Lenz G, Farinha P, Dang L, 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(7):3701–13.PubMedCrossRef

29.

Scuto A, Kujawski M, Kowolik C, Krymskaya L, Wang L, Weiss LM, et al. STAT3 inhibition is a therapeutic strategy for ABC-like diffuse large B cell lymphoma. Cancer Res. 2011;71(9):3182–8.PubMedCrossRef

30.

Kato M, Sanada M, Kato I, Sato Y, Takita J, Takeuchi K, et al. Frequent inactivation of A20 in B cell lymphomas. Nature. 2009;459(7247):712–6.PubMedCrossRef

31.

Jaffe ES, Pittaluga S. Aggressive B cell lymphomas: a review of new and old entities in the WHO classification. Hematol Am Soc Hematol Educ Program. 2011;2011:506–14.CrossRef

32.

Schmitz R, Young RM, Ceribelli M, Jhavar S, Xiao W, Zhang M, et al. Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics. Nature. 2012.

33.

Snuderl M, Kolman OK, Chen YB, Hsu JJ, Ackerman AM, Dal Cin P, et al. B cell lymphomas with concurrent IGH-BCL2 and MYC rearrangements are aggressive neoplasms with clinical and pathologic features distinct from Burkitt lymphoma and diffuse large B cell lymphoma. Am J Surg Pathol. 2010;34(3):327–40.

34.

Aukema SM, Siebert R, Schuuring E, van Imhoff GW, Kluin-Nelemans HC, Boerma EJ, et al. Double-hit B cell lymphomas. Blood. 2011;117(8):2319–31.PubMedCrossRef

35.

Johnson NA, Savage KJ, Ludkovski O, Ben-Neriah S, Woods R, Steidl C, et al. Lymphomas with concurrent BCL2 and MYC translocations: the critical factors associated with survival. Blood. 2009;114(11):2273–9.PubMedCrossRef

36.

Tomita N. BCL2 and MYC dual-hit lymphoma/leukemia. J Clin Exp Hematop. 2011;51(1):7–12.PubMedCrossRef

37.

Ruzinova MB, Caron T, Rodig SJ. Altered subcellular localization of c-Myc protein identifies aggressive B cell lymphomas harboring a c-MYC translocation. Am J Surg Pathol. 2010;34(6):882–91.PubMedCrossRef

38.

Green TM, Young KH, Visco C, Xu-Monette ZY, Orazi A, Go RS, et al. Immunohistochemical double-hit score is a strong predictor of outcome in patients with diffuse large B cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol. 2012;30(28):3460–7.PubMedCrossRef

39.

Johnson NA, Slack GW, Savage KJ, Connors JM, Ben-Neriah S, Rogic S, et al. Concurrent Expression of MYC and BCL2 in Diffuse Large B Cell Lymphoma Treated With Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone. J Clin Oncol. 2012;30(28):3452–9.PubMedCrossRef

40.

Cuccuini W, Briere J, Mounier N, Voelker HU, Rosenwald A, Sundstrom C, et al. MYC⁺ diffuse large B-cell lymphoma is not salvaged by classical R-ICE or R-DHAP followed by BEAM plus autologous stem cell transplantation. Blood. 2012;119(20):4619–24.

41.

Lam LT, Davis RE, Pierce J, Hepperle M, Xu Y, Hottelet M, et al. Small molecule inhibitors of IkappaB kinase are selectively toxic for subgroups of diffuse large B cell lymphoma defined by gene expression profiling. Clin Cancer Res. 2005;11(1):28–40.PubMed

42.

Goy A, Phase II. Study of proteasome inhibitor bortezomib in relapsed or refractory B cell non-Hodgkin’s lymphoma. J Clin Oncol. 2005;23(4):667–75.PubMedCrossRef

43.

Fisher RI, Bernstein SH, Kahl BS, Djulbegovic B, Robertson MJ, de Vos S, et al. Multicenter phase II study of bortezomib in patients with relapsed or refractory mantle cell lymphoma. J Clin Oncol. 2006;24(30):4867–74.PubMedCrossRef

44.

Strauss SJ, Higginbottom K, Juliger S, Maharaj L, Allen P, Schenkein D, et al. The proteasome inhibitor bortezomib acts independently of p53 and induces cell death via apoptosis and mitotic catastrophe in B cell lymphoma cell lines. Cancer Res. 2007;67(6):2783–90.PubMedCrossRef

45.

Mahadevan D, Fisher RI. Novel therapeutics for aggressive non-Hodgkin’s lymphoma. J Clin Oncol. 2011;29(14):1876–84.PubMedCrossRef

46.

Dunleavy K, Pittaluga S, Czuczman MS, Dave SS, Wright G, Grant N, et al. Differential efficacy of bortezomib plus chemotherapy within molecular subtypes of diffuse large B cell lymphoma. Blood. 2009;113(24):6069–76.PubMedCrossRef

47.

Ruan J, Martin P, Furman RR, Lee SM, Cheung K, Vose JM, et al. Bortezomib plus CHOP-rituximab for previously untreated diffuse large B cell lymphoma and mantle cell lymphoma. J Clin Oncol. 2011;29(6):690–7.PubMedCrossRef

48.

Chanan-Khan AA, Cheson BD. Lenalidomide for the treatment of B cell malignancies. J Clin Oncol. 2008;26(9):1544–52.PubMedCrossRef

49.

Hernandez-Ilizaliturri FJ, Deeb G, Zinzani PL, Pileri SA, Malik F, Macon WR, et al. Higher response to lenalidomide in relapsed/refractory diffuse large B cell lymphoma in nongerminal center B cell-like than in germinal center B cell-like phenotype. Cancer. 2011;117(22):5058–66.PubMedCrossRef

50.

Yang Y, Shaffer AL 3rd, Emre NC, Ceribelli M, Zhang M, Wright G, et al. Exploiting synthetic lethality for the therapy of ABC diffuse large B cell lymphoma. Cancer Cell. 2012;21(6):723–37.PubMedCrossRef

51.

Zhu YX, Braggio E, Shi CX, Bruins LA, Schmidt JE, Van Wier S, et al. Cereblon expression is required for the antimyeloma activity of lenalidomide and pomalidomide. Blood. 2011;118(18):4771–9.PubMedCrossRef

52.

Soucy TA, Smith PG, Milhollen MA, Berger AJ, Gavin JM, Adhikari S, et al. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature. 2009;458(7239):732–6.PubMedCrossRef

53.

Milhollen MA, Traore T, Adams-Duffy J, Thomas MP, Berger AJ, Dang L, et al. MLN4924, a NEDD8-activating enzyme inhibitor, is active in diffuse large B cell lymphoma models: rationale for treatment of NF-{kappa}B-dependent lymphoma. Blood. 2010;116(9):1515–23.PubMedCrossRef

54.

Gauld SB. Dal Porto JM, Cambier JC. B cell antigen receptor signaling: roles in cell development and disease. Science. 2002;296(5573):1641–2.PubMedCrossRef

55.

Chen L, Monti S, Juszczynski P, Daley J, Chen W, Witzig TE, et al. SYK-dependent tonic B cell receptor signaling is a rational treatment target in diffuse large B cell lymphoma. Blood. 2008;111(4):2230–7.PubMedCrossRef

56.

Friedberg JW, Sharman J, Sweetenham J, Johnston PB, Vose JM, Lacasce A, et al. Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia. Blood. 2010;115(13):2578–85.PubMedCrossRef

57.

Winer ES, Ingham RR, Castillo JJ. PCI-32765: a novel Bruton’s tyrosine kinase inhibitor for the treatment of lymphoid malignancies. Expert Opin Investig Drugs. 2012;21(3):355–61.PubMedCrossRef

58.

Honigberg LA, Smith AM, Sirisawad M, Verner E, Loury D, Chang B, 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(29):13075–80.PubMedCrossRef

59.

Kenkre VP, Kahl BS. The future of B cell lymphoma therapy: the B cell receptor and its downstream pathways. Curr Hematol Malig Rep. 2012;7(3):216–20.PubMedCrossRef

60.

Staudt LM, Dunleavy K, Buggy JJ, Hedrick E, Lucas N, Pittaluga S, et al. The Bruton’s Tyrosine Kinase (Btk) Inhibitor PCI-32765 Modulates Chronic Active BCR Signaling and Induces Tumor Regression in Relapsed/Refractory ABC DLBCL. ASH Annual Meeting Abstracts. 2011;118(21):2716.

61.

Shipp MA, Ross KN, Tamayo P, Weng AP, Kutok JL, Aguiar RC, et al. Diffuse large B cell lymphoma outcome prediction by gene-expression profiling and supervised machine learning. Nat Med. 2002;8(1):68–74.PubMedCrossRef

62.

Rossi RM, Henn AD, Conkling R, Guzman ML, Bushnell T, Harvey J, et al. The PKCβ selective inhibitor, enzastaurin (LY317615), inhibits growth of human lymphoma cells. ASH Annual Meeting Abstracts. 2005;106(11):1483.

63.

Robertson MJ, Kahl BS, Vose JM, de Vos S, Laughlin M, Flynn PJ, et al. Phase II study of enzastaurin, a protein kinase C beta inhibitor, in patients with relapsed or refractory diffuse large B cell lymphoma. J Clin Oncol. 2007;25(13):1741–6.PubMedCrossRef

64.

Hainsworth JD, Arrowsmith ER, Mccleod M, Fayad LE, Hamid O, Davis L, et al. Randomized phase II study of R-CHOP plus enzastaurin versus R-CHOP in the first line treatment of patients with intermediate and high-risk diffuse large B cell lymphoma (DLBCL)—preliminary analysis. Annals Oncol. 2011;22(suppl 4):(Abstract 074).

65.

Lannutti BJ, Meadows SA, Herman SEM, Kashishian A, Steiner B, Johnson AJ, et al. CAL-101, a p110 selective phosphatidylinositol-3-kinase inhibitor for the treatment of B cell malignancies, inhibits PI3K signaling and cellular viability. Blood. 2010;117(2):591–4.PubMedCrossRef

66.

Furman RR, Byrd JC, Brown JR, Coutre SE, Benson DM, Jr., Wagner-Johnston ND, et al. CAL-101, an isoform-selective inhibitor of phosphatidylinositol 3-kinase P110Δ, demonstrates clinical activity and pharmacodynamic effects in patients with relapsed or refractory chronic lymphocytic leukemia. ASH Annual Meeting Abstracts. 2010;116(21):55.

67.

Calo V, Migliavacca M, Bazan V, Macaluso M, Buscemi M, Gebbia N, et al. STAT proteins: from normal control of cellular events to tumorigenesis. J Cell Physiol. 2003;197(2):157–68.PubMedCrossRef

68.

Murray PJ. The JAK-STAT signaling pathway: input and output integration. J Immunol. 2007;178(5):2623–9.PubMed

69.

Bromberg J, Darnell JE Jr. The role of STATs in transcriptional control and their impact on cellular function. Oncogene. 2000;19(21):2468–73.PubMedCrossRef

70.

Kortylewski M, Kujawski M, Wang T, Wei S, Zhang S, Pilon-Thomas S, et al. Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent antitumor immunity. Nat Med. 2005;11(12):1314–21.PubMedCrossRef

71.

Hart S, Goh KC, Novotny-Diermayr V, Hu CY, Hentze H, Tan YC, et al. SB1518, a novel macrocyclic pyrimidine-based JAK2 inhibitor for the treatment of myeloid and lymphoid malignancies. Leukemia. 2011;25(11):1751–9.PubMedCrossRef

72.

Mascarenhas J, Hoffman R. Ruxolitinib: the first FDA approved therapy for the treatment of myelofibrosis. Clin Cancer Res. 2012;18(11):3008–14.PubMedCrossRef

73.

Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012;366(9):799–807.PubMedCrossRef

74.

Verstovsek S, Kantarjian H, Mesa RA, Pardanani AD, Cortes-Franco J, Thomas DA, et al. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med. 2010;363(12):1117–27.PubMedCrossRef

75.

Lee H, Deng J, Kujawski M, Yang C, Liu Y, Herrmann A, et al. STAT3-induced S1PR1 expression is crucial for persistent STAT3 activation in tumors. Nat Med. 2010;16(12):1421–8.PubMedCrossRef

76.

Liu Y, Deng J, Wang L, Lee H, Armstrong B, Scuto A, et al. S1PR1 is an effective target to block STAT3 signaling in activated B cell like diffuse large B cell lymphoma. Blood. 2012;120(7):1458–65.PubMedCrossRef

77.

Klampfer L, Huang J, Swaby LA, Augenlicht L. Requirement of histone deacetylase activity for signaling by STAT1. J Biol Chem. 2004;279(29):30358–68.PubMedCrossRef

78.

Gupta M, Han JJ, Stenson M, Wellik L, Witzig TE. Regulation of STAT3 by histone deacetylase-3 in diffuse large B cell lymphoma: implications for therapy. Leukemia. 2011;26(6):1356–64.PubMedCrossRef

79.

Dent AL, Shaffer AL, Yu X, Allman D, Staudt LM. Control of inflammation, cytokine expression, and germinal center formation by BCL-6. Science. 1997;276(5312):589–92.PubMedCrossRef

80.

Polo JM, Dell’Oso T, Ranuncolo SM, Cerchietti L, Beck D, Da Silva GF, et al. Specific peptide interference reveals BCL6 transcriptional and oncogenic mechanisms in B cell lymphoma cells. Nat Med. 2004;10(12):1329–35.PubMedCrossRef

81.

Phan RT, Dalla-Favera R. The BCL6 proto-oncogene suppresses p53 expression in germinal-centre B cells. Nature. 2004;432(7017):635–9.PubMedCrossRef

82.

Pasqualucci L, Migliazza A, Fracchiolla N, William C, Neri A, Baldini L, et al. BCL-6 mutations in normal germinal center B cells: evidence of somatic hypermutation acting outside Ig loci. Proc Natl Acad Sci USA. 1998;95(20):11816–21.PubMedCrossRef

83.

Colomo L, Lopez-Guillermo A, Perales M, Rives S, Martinez A, Bosch F, et al. Clinical impact of the differentiation profile assessed by immunophenotyping in patients with diffuse large B cell lymphoma. Blood. 2003;101(1):78–84.PubMedCrossRef

84.

Cerchietti LC, Ghetu AF, Zhu X, Da Silva GF, Zhong S, Matthews M, et al. A small-molecule inhibitor of BCL6 kills DLBCL cells in vitro and in vivo. Cancer Cell. 2010;17(4):400–11.PubMedCrossRef

85.

Barrans S, Crouch S, Smith A, Turner K, Owen R, Patmore R, et al. Rearrangement of MYC is associated with poor prognosis in patients with diffuse large B cell lymphoma treated in the era of rituximab. J Clin Oncol. 2010;28(20):3360–5.PubMedCrossRef

86.

Savage KJ, Johnson NA, Ben-Neriah S, Connors JM, Sehn LH, Farinha P, et al. MYC gene rearrangements are associated with a poor prognosis in diffuse large B cell lymphoma patients treated with R-CHOP chemotherapy. Blood. 2009;114(17):3533–7.PubMedCrossRef

87.

Dunleavy K, Pittaluga S, Wayne AS, Shovlin M, Johnson J, Little R, et al. MYC⁺ aggressive B cell lymphomas: novel therapy of untreated Burkitt lymphoma (BL) and MYC⁺ diffuse large B cell lymphoma (DLBCL) with DA-EPOCH-R. Annals Oncol 2011;22 (suppl 4):(Abstract 071).

88.

Delmore JE, Issa GC, Lemieux ME, Rahl PB, Shi J, Jacobs HM, et al. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011;146(6):904–17.PubMedCrossRef

89.

Chesi M, Matthews GM, Garbitt VM, Palmer SE, Shortt J, Lefebure M, et al. Drug response in a genetically engineered mouse model of multiple myeloma is predictive of clinical efficacy. Blood. 2012;120(2):376–85.PubMedCrossRef

90.

Rounbehler Robert J, Fallahi M, Yang C, Steeves Meredith A, Li W, Doherty Joanne R, et al. Tristetraprolin impairs myc-induced lymphoma and abolishes the malignant state. Cell. 2012;150(3):563–74.

91.

Hamada M, Yakushijin Y, Ohtsuka M, Kakimoto M, Yasukawa M, Fujita S. Aurora2/BTAK/STK15 is involved in cell cycle checkpoint and cell survival of aggressive non-Hodgkin’s lymphoma. Br J Haematol. 2003;121(3):439–47.PubMedCrossRef

92.

Anand S, Penrhyn-Lowe S, Venkitaraman AR. AURORA-A amplification overrides the mitotic spindle assembly checkpoint, inducing resistance to Taxol. Cancer Cell. 2003;3(1):51–62.PubMedCrossRef

93.

Padmanabhan S, Shea TC, Vose JM, Reeder CB, Berdeja JG, McDonagh KT, et al. Phase I study of an investigational Aurora A kinase inhibitor MLN8237 in patients with advanced hematologic malignancies. ASH Annual Meeting Abstracts. 2010;116(21):2799.

94.

Mahadevan D, Stejskal A, Cooke LS, Manziello A, Morales C, Persky DO, et al. Aurora A inhibitor (MLN8237) plus vincristine plus rituximab is synthetic lethal and a potential curative therapy in aggressive B cell non-Hodgkin lymphoma. Clin Cancer Res. 2012;18(8):2210–9.PubMedCrossRef

95.

Lenz G, Staudt LM. Aggressive lymphomas. N Engl J Med. 2010;362(15):1417–29.PubMedCrossRef

96.

Weniger MA, Wiestner A. Molecular targeted approaches in mantle cell lymphoma. Semin Hematol. 2011;48(3):214–26.PubMedCrossRef

Titel: Diffuse large B cell lymphoma: molecular targeted therapy
verfasst von: Mark Roschewski
Kieron Dunleavy
Wyndham H. Wilson
Publikationsdatum: 01.11.2012
Verlag: Springer Japan
Erschienen in: International Journal of Hematology / Ausgabe 5/2012
Print ISSN: 0925-5710
Elektronische ISSN: 1865-3774
DOI: https://doi.org/10.1007/s12185-012-1198-3

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