CARD11、Bcl-2和NF-κB在弥漫性大B细胞淋巴瘤中的表达与意义
|
摘要
目的:观察弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma DLBCL)中CARD11、NF-κB和Bcl-2表达情况,探讨它们在弥漫性大B细胞淋巴瘤中不同免疫分型中表达的意义及相互关系。
方法:选取弥漫性大B细胞淋巴瘤60例和反应性增生的淋巴结20例,本组病例手术前均未经放疗和化疗。采用组织芯片技术和免疫组织化学方法对弥漫性大B细胞淋巴瘤进行免疫分型并检测弥漫性大B细胞淋巴瘤免疫学类型GCB和ABC型中CARD11、NF-κB和Bcl-2表达情况。结果:①60例弥漫性大B细胞淋巴瘤CD10、Bcl-6、MUM1和CD138的阳性表达率分别为30.0%、58.3%、58.3%、1.7%。②免疫分型: 60例弥漫性大B细胞淋巴瘤中免疫类型GCB25例,ABC35例。GCB25例中CD10(+)/Bcl-6(+)14例,CD10(-)/Bcl-6(+)1例; ABC35例中CD10(-)/bcl-6(-)21例, CD10(-)/Bcl-6(+)14例,MUM1(+)/CD138 ( - ) 13例, MUM1(+)/CD138(+)1例。③60例弥漫性大B细胞淋巴瘤中免疫类型中CARD11、Bcl-2和NF-κB表达情况:免疫类型GCB中CARD11的阳性率为24.0%,ABC中CARD11的阳性率为57.4%,二者之间P<0.05;GCB中Bcl-2的阳性率为32.0%,ABC中Bcl-2的阳性率为62.9%,二者之间P<0.05;GCB中NF-κB的阳性率为28.0%,ABC中NF-κB的阳性率为68.6%,二者之间P<0.05。CARD11阳性弥漫性大B细胞淋巴瘤中Bcl-2阳性率为80.8%, CARD11阴性弥漫性大B细胞淋巴瘤中Bcl-2阳性率为26.5%,二者之间P<0.05;NF-κB阳性弥漫性大B细胞淋巴瘤中Bcl-2阳性率为58.1%,NF-κB阴性弥漫性大B细胞淋巴瘤中Bcl-2阳性率为41.0%,二者之间P<0.05;CARD11阳性弥漫性大B细胞淋巴瘤中NF-κB阳性率为76.9%,CARD11阴性弥漫性大B细胞淋巴瘤中NF-κB阳性率为32.4%,二者之间P<0.05;结论:①CARD11、Bcl-2、NF-κB高表达与弥漫性大B细胞淋巴瘤的ABC类型相关。②CARD11、Bcl-2、NF-κB的表达相互之间存在正相关。
Objective: To study the expression and significance of CARD11、Bcl-2、NF-κB in the common immunology types of diffuse large B-cell lymphoma and explore the correlativity during them.
Materials and Methods: 60 specimens of diffuse large B-cell lymphoma patients and 20 specimens of reactive hyperplasia lymph node were selected, CARD11,Bcl-2 and NF-κB were studied by using tissue chip technique and the MaxVision immunohistochemical methods.
Results:①The positive rates of CD10,Bcl-6,MUM1 and CD138 in 60 specimens of diffuse large B-cell lymphoma patients were 30.0%、58.3% ,58.3% and 1.7% respectively.②In 60 specimens of diffuse large B-cell lymphoma patients. immunology type: GCB 25 cases, ABC35 cases. 14 cases had the profile CD10(+)/bcl-6(+) and 11 cases had the profileCD10(-)/Bcl-6(+) , 21 cases had the profile CD10(-)/Bcl-6(-), 13 cases had the profile CD10(-) /bcl-6(+)/MUM1(+)/CD138(-) and 1 case had the profile CD10(-)/Bcl-6(+)/MUM1 (+) /CD138(+).③In 60 specimens of diffuse large B-cell lymphoma patients. Immunology type: GCB 25 cases, ABC 35 cases. GCB 25 cases, the positive rates of CARD 11was 24.0% ,ABC 35 cases, the positive rates of CARD11 was57.4%, there being significant difference between the two groups(P<0.05); GCB 25 cases, the positive rates of Bcl-2 was32.0% ,ABC35 cases, the positive rates of Bcl-2 was 62.9%, there being significant difference between the two groups(P<0.05); GCB 25 cases, the positive rates of NF-κB was 28.0% ,ABC 35 cases, the positive rates of NF-κB was 68.6%, there being significant difference between the two groups(P<0.05); The positive rates of Bcl-2 in CARD11 positive and native specimens were 80.8%、26.5% respectively, there being significant difference between the two groups( P<0.05). The positive rates of Bcl-2 in NF-κB positive and native specimens were 58.1%、41.0% respectively, there being significant difference between the two groups( P<0.05). The positive rates of NF-κB in CARD11 positive and native specimens were 76.9%、32.4% respectively, there being significant difference between the two groups( P<0.05).
Conclusion: 1、The high expression of CARD11、NF-κB and bcl-2 were related to ABC immunology type of diffuse large B-cell lymphoma ; 2、There is significant positive correlation between CARD11 and Bcl-2, CARD11 and NF-κB, Bcl-2 and NF-κB , respectively.
方法:选取弥漫性大B细胞淋巴瘤60例和反应性增生的淋巴结20例,本组病例手术前均未经放疗和化疗。采用组织芯片技术和免疫组织化学方法对弥漫性大B细胞淋巴瘤进行免疫分型并检测弥漫性大B细胞淋巴瘤免疫学类型GCB和ABC型中CARD11、NF-κB和Bcl-2表达情况。结果:①60例弥漫性大B细胞淋巴瘤CD10、Bcl-6、MUM1和CD138的阳性表达率分别为30.0%、58.3%、58.3%、1.7%。②免疫分型: 60例弥漫性大B细胞淋巴瘤中免疫类型GCB25例,ABC35例。GCB25例中CD10(+)/Bcl-6(+)14例,CD10(-)/Bcl-6(+)1例; ABC35例中CD10(-)/bcl-6(-)21例, CD10(-)/Bcl-6(+)14例,MUM1(+)/CD138 ( - ) 13例, MUM1(+)/CD138(+)1例。③60例弥漫性大B细胞淋巴瘤中免疫类型中CARD11、Bcl-2和NF-κB表达情况:免疫类型GCB中CARD11的阳性率为24.0%,ABC中CARD11的阳性率为57.4%,二者之间P<0.05;GCB中Bcl-2的阳性率为32.0%,ABC中Bcl-2的阳性率为62.9%,二者之间P<0.05;GCB中NF-κB的阳性率为28.0%,ABC中NF-κB的阳性率为68.6%,二者之间P<0.05。CARD11阳性弥漫性大B细胞淋巴瘤中Bcl-2阳性率为80.8%, CARD11阴性弥漫性大B细胞淋巴瘤中Bcl-2阳性率为26.5%,二者之间P<0.05;NF-κB阳性弥漫性大B细胞淋巴瘤中Bcl-2阳性率为58.1%,NF-κB阴性弥漫性大B细胞淋巴瘤中Bcl-2阳性率为41.0%,二者之间P<0.05;CARD11阳性弥漫性大B细胞淋巴瘤中NF-κB阳性率为76.9%,CARD11阴性弥漫性大B细胞淋巴瘤中NF-κB阳性率为32.4%,二者之间P<0.05;结论:①CARD11、Bcl-2、NF-κB高表达与弥漫性大B细胞淋巴瘤的ABC类型相关。②CARD11、Bcl-2、NF-κB的表达相互之间存在正相关。
Objective: To study the expression and significance of CARD11、Bcl-2、NF-κB in the common immunology types of diffuse large B-cell lymphoma and explore the correlativity during them.
Materials and Methods: 60 specimens of diffuse large B-cell lymphoma patients and 20 specimens of reactive hyperplasia lymph node were selected, CARD11,Bcl-2 and NF-κB were studied by using tissue chip technique and the MaxVision immunohistochemical methods.
Results:①The positive rates of CD10,Bcl-6,MUM1 and CD138 in 60 specimens of diffuse large B-cell lymphoma patients were 30.0%、58.3% ,58.3% and 1.7% respectively.②In 60 specimens of diffuse large B-cell lymphoma patients. immunology type: GCB 25 cases, ABC35 cases. 14 cases had the profile CD10(+)/bcl-6(+) and 11 cases had the profileCD10(-)/Bcl-6(+) , 21 cases had the profile CD10(-)/Bcl-6(-), 13 cases had the profile CD10(-) /bcl-6(+)/MUM1(+)/CD138(-) and 1 case had the profile CD10(-)/Bcl-6(+)/MUM1 (+) /CD138(+).③In 60 specimens of diffuse large B-cell lymphoma patients. Immunology type: GCB 25 cases, ABC 35 cases. GCB 25 cases, the positive rates of CARD 11was 24.0% ,ABC 35 cases, the positive rates of CARD11 was57.4%, there being significant difference between the two groups(P<0.05); GCB 25 cases, the positive rates of Bcl-2 was32.0% ,ABC35 cases, the positive rates of Bcl-2 was 62.9%, there being significant difference between the two groups(P<0.05); GCB 25 cases, the positive rates of NF-κB was 28.0% ,ABC 35 cases, the positive rates of NF-κB was 68.6%, there being significant difference between the two groups(P<0.05); The positive rates of Bcl-2 in CARD11 positive and native specimens were 80.8%、26.5% respectively, there being significant difference between the two groups( P<0.05). The positive rates of Bcl-2 in NF-κB positive and native specimens were 58.1%、41.0% respectively, there being significant difference between the two groups( P<0.05). The positive rates of NF-κB in CARD11 positive and native specimens were 76.9%、32.4% respectively, there being significant difference between the two groups( P<0.05).
Conclusion: 1、The high expression of CARD11、NF-κB and bcl-2 were related to ABC immunology type of diffuse large B-cell lymphoma ; 2、There is significant positive correlation between CARD11 and Bcl-2, CARD11 and NF-κB, Bcl-2 and NF-κB , respectively.
引文
[1] Armitage JO, Weisenburger DD, New approach to classifying non-Hodgkin’s lymphomas: clinical features of the major histologic subtypes. Non- Hodgkin’s lymphoma lymphoma classification project. [J] clin Oncol 1998;16(8):2780-2795.
[2] Coiffier B.Diffuse large cell lymphoma.Curr Opin Oncol,2001,13:325 334.
[3] Alizadeh AA,Eisen MB,Davis RE, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling.[J]. Nature 2000,403 (6769):503-511.
[4] Hans C P,WeisenBurger D D,GreinerTC,et al.Confirmation of the molecular classification of diffuse large B cell lymphoma By immunohistochemistry using a tissue microarray. Blood,2004,103:275 282.
[5] Betin J,Wang L,Guo Y et al. CARD11 and CARD14 are novel caspase recruitment domain (CARD)/membrane-associated guanylate kinase (MAGUK) family members that interact with BCL10 and activate NF-kappa B.J Biol Chem. 2001 ;276(15):11877-82.
[6] Ngo VN, Davis RE, Lamy L et al. A loss-of-function RNA interference screen for molecular targets in cancer[J]. Nature. 2006 ;441(7089):106-110.
[7] Sen R,Baltimore D.Multiple nuclear factors interact with the immunoglobulin enhancer sequences.Cell 1986;46:705-716.
[8] Kucharczak J, Simmons MJ, Fan Y, et al. To be,or not to be: NF-κB is the answer-role of Rel/ NF-κB in the regulation of apoptosis.[J] Oncogene 2003;22(56):8961-8982.
[9] Karin M, Cao Y, Greten FR,et al. NF-kappaB in cancer: from innocent bystander to major culprit.[J]. Nat Rev Cancer. 2002 ;2(4):301-310.
[10] Baldwin AS. Control of oncogenesis and cancer therapy resistance by the transcription factor NF-kappaB,[J]. Clin Invest. 2001 ;107(3):241-246.
[11] Tracey L,Perez-Rosado A,Artiga MJ et al. Expression of the NF-kappaB targets BCL2 and BIRC5/Survivin characterizes small B-cell and aggressive B-cell lymphomas, respectively. J Pathol. 2005 ;206(2):123-34.
[12] Davis RE,Brown KD, Siebenlist U et al. 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.
[13] Kim SW,Oleksyn DW,Rossi RM et al. Protein kinase C-associated kinase PKK is required for NF-{kappa}B signaling and survival in diffuse large B-cell lymphoma cells. Blood. 2007 Nov 19; [Epub ahead of print]
[14] Lam LT, Davis RE, Pierce J et al. Small molecule inhibitors of IkappaB kinase are selectively toxic for subgroups of diffuse large B-cell lymphoma defined by gene expression profiling.[J] Clin Cancer Res. 2005 ;11(1):28-40.
[15] Bai M, Skyrlas A, Agnantis NJ et al. Diffuse large B-cell lymphomas with germinal centerB-cell-like differentiation immunophenotypic profile are associated with high apoptotic index, high expression of the proapoptotic proteins bax, bak and bid and low expression of the antiapoptotic protein bcl-xl. Mod Pathol. 2004 ;17(7):847-56
[16] Pedro F,Gwyn B,Reiner S et al. Mechanisms of Bcl-2 Protein Expression in diffuse large B-cell lymphoma (DLBCL).Blood. 2004;104;26.
[17]许良中,杨文涛.免疫组织化学反应结果的判断标准[J].中国癌症杂志,1996,6(4).
[18] 黄忠连,顾康生,孟刚。Bcl-2 与 N F-κB/p 65 在弥漫性大 B 细胞淋巴瘤中的表达及 意义。山东医药[J],2007.47(4):3-4.
[19] Wang D, You Y, Case SM, et al. A requirement for CARM1 in TCR-induced NF-kB activation.Nat Immunol.2002;3:830-835.
[20] Gaide O,Favier B,Legler DF,et al. CARM1 is a critical lipid raft-associated regulator of TCR-induced NF-kB activation Nat Immunol.2002;3:836-843.
[21] Hara H, Wada T, Bakal L, et al. The MAGUK protein CARD11 is essential for lymphocyte activation . Immunity. 2003;18:763-775.
[22] Ruefli-Brasse AA, French DM, Dixit VM. Regulation of NF-kB-dependent lymphocyte activation and development by para caspase.Science.2003;302:1581-1584.
[23] Shigeo N, Shoturo N, Takayuki M. et al. Overexpression of Caspase Recruitment Domain(CARD) Membrane-Associated Guanylate Kinase 1 (CARMA1) and CARD9 in Primary Gastric B-cell lymphoma Cancer 2005.104(9):1885-1893.
[24] Thome M. CARMA1, BCL-10 and MALT1 in lymphocyte development and activation[J]. Nat Rev Immunol. 2004 ;4(5):348-359.
[25] Lenz G, Davis RE, Ngo VN et al. Oncogenic CARD11 mutations in human diffuse large B cell lymphoma.Science. 2008 ;319(5870):1676-9.
[26] Sen R, Batimore D, Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell 1986; 46:705-716.
[27] Shishodia S, Majymdar S, Banerjee S, et al.Ursolic acid inhibits nuclear factor-kappa B activation induced by carcinogeinc agents through suppression of I kappa B alpha kinase and p65 phosphorylation:correlation with down-regulation of cyclooxygenase 2, matrixmetall- oproteinase 9,and cyclin D1. Cancer Res.2003;63(15):4375-4383.
[28] Silverman N, Maniatis T. NF-kappa B signaling pathways in mammalian and innate immunity. Gens Dev 2001;15(18):2321-2342.
[29] Nkayama H, Ikebe T, Beppu M,et al. High expression levels of nuclear factor kappaB, IkappaB kinase alpha and Akt kinase in squamous cell carcinoma of the oral cavity.Cancer. 2001 ;92(12):3037-44.
[30] Loercher A, Lee TL, Ricker TL, et al. Nuclear factor-kappaB is an important modulator of the altered gene expression profile and malignant phenotype in squamous cell carcinoma. Cancer Res. 2004;64(18):6511-6523.
[31] Yu HG, Yu LL, Yang Y,et al. Increased expression of RelA/nuclear factor-kappa B protein correlates with colorectal tumorigenesis. Oncology. 2003;65(1):37-45.
[32] Viatour P, Bentires-Alj M,Chariot A, NF- kappa B2/p100 induces Bcl-2 expression. Leukemia. 2003:17(7):1349-1356.
[33] Bentires-Alj M,Barbu R,Fillet M,et al. NF-kappaB transcription factor induces drug resistance through MDR1 expression in cancer cells.Oncogene. 2003 ;22(1):90-7.
[34] Veston VJ, Austen B, Wei W, et al.Apoptotic resistance to ionizing radiation in pediatric B-precursor acute lymphoblastic leukemia frequently involves increased NF-kappaB survival pathway signaling. Blood. 2004 ;104(5):1465-73.
[35] Lam LT, Davis RE, Pierce J et al. Small molecule inhibitors of IkappaB kinase are selectively toxic for subgroups of diffuse large B-cell lymphoma defined by gene expression profiling.[J] Clin Cancer Res. 2005 ;11(1):28-40.
[36] Brown R. The Bcl-2 family of proteins.British Medical Bulletin, 1996.;53:466-477
[37] Poulsen CB,Hansen M,et al. Profiling of diffuse large B-cell lymphoma by immunohis- tochemistry: identification of prognostic subgroups.Eur J Haematol. 2007 ;79(6):501-7.
[38] Eow GI,Kim LH,Pehsc. The pattern of CD15, CD30 and Bcl-2 expression in diffuse large B-cell lymphoma. Med J Malaysia. 2006 ;61(4):416-21。
[39] Shivakumar L,Armitage JO. Bcl-2 gene expression as a predictor of outcome in diffuse large B-cell lymphoma. Clin Lymphoma Myeloma. 2006 ;6(6):455-7.
[40] Bai M, Skyrlas A, Agnantis NJ et al. Cluster analysis of apoptosis-associated bcl2 family proteins in diffuse large B-cell lymphomas. Relations with the apoptotic index, the proliferation profile and the B-cell differentiation immunophenotypes. Anticancer Res. 2004 ; 24(5A):3081-8
[41] Bai M, Skyrlas A, Agnantis NJ et al. Diffuse large B-cell lymphomas with germinal center B-cell-like differentiation immunophenotypic profile are associated with high apoptotic index, high expression of the proapoptotic proteins bax, bak and bid and low expression of the antiapoptotic protein bcl-xl. Mod Pathol. 2004 ;17(7):847-56
[42] Pedro F,Gwyn B,Reiner S et al. Mechanisms of Bcl-2 Protein Expression in diffuse large B-cell lymphoma (DLBCL).Blood. 2004;104;26.
[1] Armitage JO, Weisenburger DD, New approach to classifying non-Hodgkin’s lymphomas: clinical features of the major histologic subtypes. Non- Hodgkin’s lymphoma lymphoma classification project. [J] clin Oncol 1998;16(8):2780-2795.
[2] Coiffier B. Diffuse large B-cell lymphoma . Curr opin Oncol. 2001; 13(5):325-334.
[3] Harris NL, Jaffe ES, Stein H, et al , A revised European-American classifiction of lymphoidneoplasm:a proposal from the International lymphoma, Study Group [J].Blood, 1994, 84(5): 1361-1392.
[4] Jaffe ES, Harris NL, Stein H et al, WHO Classifiction of tuomors .Pathology and genetics of tumors of haematopoietic and lymphoid tissues [M].lyon: LARC Press ,2001:171-180.
[5] Colomo L,Loong F,Rives S et al. Diffuse large B-cell lymphomas with plasmablastic differentiation represent a heterogeneous group of disease entities.Am J Surg Pathol 2004;28 (6):736-747.
[6] Wang J,Sun NC,Chen YY et al. T-cell/histiocyte-rich large B-cell lymphoma displays a heterogeneity similar to diffuse large B-cell lymphoma: a clinicopathologic, immunohistoch- emical, and molecular study of 30 cases.Appl Immunohistochem Mol Morphol.[J].2005; 13(2):109-115.
[7] Boleti E,Johnson PW. Primary mediastinal B-cell lymphoma.Hematol Oncol. 2007 [Epub ahead of print].
[8] Murase T,Yamaguchi M,Suzuki R et al. Intravascular large B-cell lymphoma (IVLBCL): a clinicopathologic study of 96 cases with special reference to the immunophenotypic heterogeneity of CD5.[J].Blood 2007; 109(2):478-485.
[9] 朱雄增. 弥漫性大 B 细胞淋巴瘤研究进展.临床与实验病理学杂志.[J] 2005,20(3): 262-265。
[10] Bosga-bouwer AG,Kok K,Booman M et al. Array comparative genomic hybridization reveals a very high frequency of deletions of the long arm of chromosome 6 in testicular lymphoma.[J]. Genes Chromosomes Cancer. 2006 ;45(10):976-81
[11] Gascoyne RD, Lamant L, Martin-Subero JI et al. ALK-positive diffuse large B-cell lymphoma is associated with Clathrin-ALK rearrangements: report of 6 cases.[J]. Blood. 2003 ;102(7):2568-73.
[12] 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 bcl-2,KI-67–expression- based survival prediction.[J] Blood,2005, 106(9):3183-3190.
[13] Tagawa H, Suguro M, Tsuzuki S et al.Comparison of genome profiles for identification of diffuse large B-cell lymphoma.[J].Blood 2005,106(5):1770-1777.
[14] Anonymous, A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin’s lymphoma. The non-Hodgkin’s lymphoma classifiction project [J]. Blood,1997,89(11):3909-3918.
[15] Alizadeh AA,Eisen MB,Davis RE, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling.[J]. Nature 2000,403 (6769):503-511.
[16] Rosenwald A,Wright G, Chan WC, et al. The use of molecular profiling to predict survival after chemotherapy for diffuse large B-cell lymphoma [J]. N Engl J Med, 2002,346(25): 1937-1947.
[17] Hans CP, Denis D, Weisenburger et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarry.[J]. Blood2003,103(1):275-282.
[18] 刘艳辉 李丽 刘刚等.弥漫性大 B 细胞淋巴瘤基因表达谱的初步研究.中华病理学杂志[J]2007 .36(2):79-83。
[19] 刘勇, 路名芝, 张文书.弥漫性大 B 细胞淋巴瘤不同免疫类型中 bcl-2,KI-67 的表达及相互关系 临床与实验病理学杂志[J] 2007; 23(3):369-370。
[20] Nelms K, Huang H, Ryan J et al. Interleukin-4 receptor signaling mechanisms and their biological significance. Adv Exp Med Biol. 1998; 452:37-43.
[21] Xiaoqing L ,Hovav, Nechushtan, et al. Disticnt IL-4 induced gene expression, proliferation, and intracellular signaling in germinal center B-cell-like and activated B-cell-like diffiuse large B-cell lymphomas.[J] Blood 2005,105(7):2924-2932.
[22] Smith PG, Wang F, Wilkinson KN, et al. The phosphodiesterase PDE4B limits cAMP- associated PI3K/AKT-dependent apoptosis in diffuse large B-cell lymphoma.[J] Blood. 2005 ;105(1):308-316.
[23] Kucharczak J, Simmons MJ, Fan Y, et al. To be,or not to be: NF-κB is the answer-role of Rel/ NF-κB in the regulation of apoptosis.[J] Oncogene 2003;22(56):8961-8982.
[24] Karin M, Cao Y, Greten FR,et al. NF-kappaB in cancer: from innocent bystander to major culprit.[J]. Nat Rev Cancer. 2002 ;2(4):301-310.
[25] Baldwin AS. Control of oncogenesis and cancer therapy resistance by the transcription factor NF-kappaB,[J]. Clin Invest. 2001 ;107(3):241-246.
[26] Davis RE,Brown KD, Siebenlist U et al. 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.
[27] Lam LT, Davis RE, Pierce J et al. Small molecule inhibitors of IkappaB kinase are selectively toxic for subgroups of diffuse large B-cell lymphoma defined by gene expression profiling.[J] Clin Cancer Res. 2005 ;11(1):28-40.
[28] Tzankov A, Pehrs AC, Zimpfer A et al. Prognostic significance of CD44 expression in diffuse large B cell lymphoma of activated and germinal centre B cell-like types: a tissue microarray analysis of 90 cases.[J] Clin Pathol. 2003 ;56(10):747-52.
[29] Bertin J,Wang L, Guo Y et al. CARD11 and CARD14 are novel caspase recruitment domain (CARD)/membrane-associated guanylate kinase (MAGUK) family members that interact with BCL10 and activate NF-kappa B.[J]. Biol Chem. 2001;276(15):11877-11882.
[30] Ngo VN, Davis RE, Lamy L et al. A loss-of-function RNA interference screen for molecular targets in cancer[J]. Nature. 2006 ;441(7089):106-110.
[31] Thome M. CARMA1, BCL-10 and MALT1 in lymphocyte development and activation[J]. Nat Rev Immunol. 2004 ;4(5):348-359.
[2] Coiffier B.Diffuse large cell lymphoma.Curr Opin Oncol,2001,13:325 334.
[3] Alizadeh AA,Eisen MB,Davis RE, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling.[J]. Nature 2000,403 (6769):503-511.
[4] Hans C P,WeisenBurger D D,GreinerTC,et al.Confirmation of the molecular classification of diffuse large B cell lymphoma By immunohistochemistry using a tissue microarray. Blood,2004,103:275 282.
[5] Betin J,Wang L,Guo Y et al. CARD11 and CARD14 are novel caspase recruitment domain (CARD)/membrane-associated guanylate kinase (MAGUK) family members that interact with BCL10 and activate NF-kappa B.J Biol Chem. 2001 ;276(15):11877-82.
[6] Ngo VN, Davis RE, Lamy L et al. A loss-of-function RNA interference screen for molecular targets in cancer[J]. Nature. 2006 ;441(7089):106-110.
[7] Sen R,Baltimore D.Multiple nuclear factors interact with the immunoglobulin enhancer sequences.Cell 1986;46:705-716.
[8] Kucharczak J, Simmons MJ, Fan Y, et al. To be,or not to be: NF-κB is the answer-role of Rel/ NF-κB in the regulation of apoptosis.[J] Oncogene 2003;22(56):8961-8982.
[9] Karin M, Cao Y, Greten FR,et al. NF-kappaB in cancer: from innocent bystander to major culprit.[J]. Nat Rev Cancer. 2002 ;2(4):301-310.
[10] Baldwin AS. Control of oncogenesis and cancer therapy resistance by the transcription factor NF-kappaB,[J]. Clin Invest. 2001 ;107(3):241-246.
[11] Tracey L,Perez-Rosado A,Artiga MJ et al. Expression of the NF-kappaB targets BCL2 and BIRC5/Survivin characterizes small B-cell and aggressive B-cell lymphomas, respectively. J Pathol. 2005 ;206(2):123-34.
[12] Davis RE,Brown KD, Siebenlist U et al. 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.
[13] Kim SW,Oleksyn DW,Rossi RM et al. Protein kinase C-associated kinase PKK is required for NF-{kappa}B signaling and survival in diffuse large B-cell lymphoma cells. Blood. 2007 Nov 19; [Epub ahead of print]
[14] Lam LT, Davis RE, Pierce J et al. Small molecule inhibitors of IkappaB kinase are selectively toxic for subgroups of diffuse large B-cell lymphoma defined by gene expression profiling.[J] Clin Cancer Res. 2005 ;11(1):28-40.
[15] Bai M, Skyrlas A, Agnantis NJ et al. Diffuse large B-cell lymphomas with germinal centerB-cell-like differentiation immunophenotypic profile are associated with high apoptotic index, high expression of the proapoptotic proteins bax, bak and bid and low expression of the antiapoptotic protein bcl-xl. Mod Pathol. 2004 ;17(7):847-56
[16] Pedro F,Gwyn B,Reiner S et al. Mechanisms of Bcl-2 Protein Expression in diffuse large B-cell lymphoma (DLBCL).Blood. 2004;104;26.
[17]许良中,杨文涛.免疫组织化学反应结果的判断标准[J].中国癌症杂志,1996,6(4).
[18] 黄忠连,顾康生,孟刚。Bcl-2 与 N F-κB/p 65 在弥漫性大 B 细胞淋巴瘤中的表达及 意义。山东医药[J],2007.47(4):3-4.
[19] Wang D, You Y, Case SM, et al. A requirement for CARM1 in TCR-induced NF-kB activation.Nat Immunol.2002;3:830-835.
[20] Gaide O,Favier B,Legler DF,et al. CARM1 is a critical lipid raft-associated regulator of TCR-induced NF-kB activation Nat Immunol.2002;3:836-843.
[21] Hara H, Wada T, Bakal L, et al. The MAGUK protein CARD11 is essential for lymphocyte activation . Immunity. 2003;18:763-775.
[22] Ruefli-Brasse AA, French DM, Dixit VM. Regulation of NF-kB-dependent lymphocyte activation and development by para caspase.Science.2003;302:1581-1584.
[23] Shigeo N, Shoturo N, Takayuki M. et al. Overexpression of Caspase Recruitment Domain(CARD) Membrane-Associated Guanylate Kinase 1 (CARMA1) and CARD9 in Primary Gastric B-cell lymphoma Cancer 2005.104(9):1885-1893.
[24] Thome M. CARMA1, BCL-10 and MALT1 in lymphocyte development and activation[J]. Nat Rev Immunol. 2004 ;4(5):348-359.
[25] Lenz G, Davis RE, Ngo VN et al. Oncogenic CARD11 mutations in human diffuse large B cell lymphoma.Science. 2008 ;319(5870):1676-9.
[26] Sen R, Batimore D, Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell 1986; 46:705-716.
[27] Shishodia S, Majymdar S, Banerjee S, et al.Ursolic acid inhibits nuclear factor-kappa B activation induced by carcinogeinc agents through suppression of I kappa B alpha kinase and p65 phosphorylation:correlation with down-regulation of cyclooxygenase 2, matrixmetall- oproteinase 9,and cyclin D1. Cancer Res.2003;63(15):4375-4383.
[28] Silverman N, Maniatis T. NF-kappa B signaling pathways in mammalian and innate immunity. Gens Dev 2001;15(18):2321-2342.
[29] Nkayama H, Ikebe T, Beppu M,et al. High expression levels of nuclear factor kappaB, IkappaB kinase alpha and Akt kinase in squamous cell carcinoma of the oral cavity.Cancer. 2001 ;92(12):3037-44.
[30] Loercher A, Lee TL, Ricker TL, et al. Nuclear factor-kappaB is an important modulator of the altered gene expression profile and malignant phenotype in squamous cell carcinoma. Cancer Res. 2004;64(18):6511-6523.
[31] Yu HG, Yu LL, Yang Y,et al. Increased expression of RelA/nuclear factor-kappa B protein correlates with colorectal tumorigenesis. Oncology. 2003;65(1):37-45.
[32] Viatour P, Bentires-Alj M,Chariot A, NF- kappa B2/p100 induces Bcl-2 expression. Leukemia. 2003:17(7):1349-1356.
[33] Bentires-Alj M,Barbu R,Fillet M,et al. NF-kappaB transcription factor induces drug resistance through MDR1 expression in cancer cells.Oncogene. 2003 ;22(1):90-7.
[34] Veston VJ, Austen B, Wei W, et al.Apoptotic resistance to ionizing radiation in pediatric B-precursor acute lymphoblastic leukemia frequently involves increased NF-kappaB survival pathway signaling. Blood. 2004 ;104(5):1465-73.
[35] Lam LT, Davis RE, Pierce J et al. Small molecule inhibitors of IkappaB kinase are selectively toxic for subgroups of diffuse large B-cell lymphoma defined by gene expression profiling.[J] Clin Cancer Res. 2005 ;11(1):28-40.
[36] Brown R. The Bcl-2 family of proteins.British Medical Bulletin, 1996.;53:466-477
[37] Poulsen CB,Hansen M,et al. Profiling of diffuse large B-cell lymphoma by immunohis- tochemistry: identification of prognostic subgroups.Eur J Haematol. 2007 ;79(6):501-7.
[38] Eow GI,Kim LH,Pehsc. The pattern of CD15, CD30 and Bcl-2 expression in diffuse large B-cell lymphoma. Med J Malaysia. 2006 ;61(4):416-21。
[39] Shivakumar L,Armitage JO. Bcl-2 gene expression as a predictor of outcome in diffuse large B-cell lymphoma. Clin Lymphoma Myeloma. 2006 ;6(6):455-7.
[40] Bai M, Skyrlas A, Agnantis NJ et al. Cluster analysis of apoptosis-associated bcl2 family proteins in diffuse large B-cell lymphomas. Relations with the apoptotic index, the proliferation profile and the B-cell differentiation immunophenotypes. Anticancer Res. 2004 ; 24(5A):3081-8
[41] Bai M, Skyrlas A, Agnantis NJ et al. Diffuse large B-cell lymphomas with germinal center B-cell-like differentiation immunophenotypic profile are associated with high apoptotic index, high expression of the proapoptotic proteins bax, bak and bid and low expression of the antiapoptotic protein bcl-xl. Mod Pathol. 2004 ;17(7):847-56
[42] Pedro F,Gwyn B,Reiner S et al. Mechanisms of Bcl-2 Protein Expression in diffuse large B-cell lymphoma (DLBCL).Blood. 2004;104;26.
[1] Armitage JO, Weisenburger DD, New approach to classifying non-Hodgkin’s lymphomas: clinical features of the major histologic subtypes. Non- Hodgkin’s lymphoma lymphoma classification project. [J] clin Oncol 1998;16(8):2780-2795.
[2] Coiffier B. Diffuse large B-cell lymphoma . Curr opin Oncol. 2001; 13(5):325-334.
[3] Harris NL, Jaffe ES, Stein H, et al , A revised European-American classifiction of lymphoidneoplasm:a proposal from the International lymphoma, Study Group [J].Blood, 1994, 84(5): 1361-1392.
[4] Jaffe ES, Harris NL, Stein H et al, WHO Classifiction of tuomors .Pathology and genetics of tumors of haematopoietic and lymphoid tissues [M].lyon: LARC Press ,2001:171-180.
[5] Colomo L,Loong F,Rives S et al. Diffuse large B-cell lymphomas with plasmablastic differentiation represent a heterogeneous group of disease entities.Am J Surg Pathol 2004;28 (6):736-747.
[6] Wang J,Sun NC,Chen YY et al. T-cell/histiocyte-rich large B-cell lymphoma displays a heterogeneity similar to diffuse large B-cell lymphoma: a clinicopathologic, immunohistoch- emical, and molecular study of 30 cases.Appl Immunohistochem Mol Morphol.[J].2005; 13(2):109-115.
[7] Boleti E,Johnson PW. Primary mediastinal B-cell lymphoma.Hematol Oncol. 2007 [Epub ahead of print].
[8] Murase T,Yamaguchi M,Suzuki R et al. Intravascular large B-cell lymphoma (IVLBCL): a clinicopathologic study of 96 cases with special reference to the immunophenotypic heterogeneity of CD5.[J].Blood 2007; 109(2):478-485.
[9] 朱雄增. 弥漫性大 B 细胞淋巴瘤研究进展.临床与实验病理学杂志.[J] 2005,20(3): 262-265。
[10] Bosga-bouwer AG,Kok K,Booman M et al. Array comparative genomic hybridization reveals a very high frequency of deletions of the long arm of chromosome 6 in testicular lymphoma.[J]. Genes Chromosomes Cancer. 2006 ;45(10):976-81
[11] Gascoyne RD, Lamant L, Martin-Subero JI et al. ALK-positive diffuse large B-cell lymphoma is associated with Clathrin-ALK rearrangements: report of 6 cases.[J]. Blood. 2003 ;102(7):2568-73.
[12] 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 bcl-2,KI-67–expression- based survival prediction.[J] Blood,2005, 106(9):3183-3190.
[13] Tagawa H, Suguro M, Tsuzuki S et al.Comparison of genome profiles for identification of diffuse large B-cell lymphoma.[J].Blood 2005,106(5):1770-1777.
[14] Anonymous, A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin’s lymphoma. The non-Hodgkin’s lymphoma classifiction project [J]. Blood,1997,89(11):3909-3918.
[15] Alizadeh AA,Eisen MB,Davis RE, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling.[J]. Nature 2000,403 (6769):503-511.
[16] Rosenwald A,Wright G, Chan WC, et al. The use of molecular profiling to predict survival after chemotherapy for diffuse large B-cell lymphoma [J]. N Engl J Med, 2002,346(25): 1937-1947.
[17] Hans CP, Denis D, Weisenburger et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarry.[J]. Blood2003,103(1):275-282.
[18] 刘艳辉 李丽 刘刚等.弥漫性大 B 细胞淋巴瘤基因表达谱的初步研究.中华病理学杂志[J]2007 .36(2):79-83。
[19] 刘勇, 路名芝, 张文书.弥漫性大 B 细胞淋巴瘤不同免疫类型中 bcl-2,KI-67 的表达及相互关系 临床与实验病理学杂志[J] 2007; 23(3):369-370。
[20] Nelms K, Huang H, Ryan J et al. Interleukin-4 receptor signaling mechanisms and their biological significance. Adv Exp Med Biol. 1998; 452:37-43.
[21] Xiaoqing L ,Hovav, Nechushtan, et al. Disticnt IL-4 induced gene expression, proliferation, and intracellular signaling in germinal center B-cell-like and activated B-cell-like diffiuse large B-cell lymphomas.[J] Blood 2005,105(7):2924-2932.
[22] Smith PG, Wang F, Wilkinson KN, et al. The phosphodiesterase PDE4B limits cAMP- associated PI3K/AKT-dependent apoptosis in diffuse large B-cell lymphoma.[J] Blood. 2005 ;105(1):308-316.
[23] Kucharczak J, Simmons MJ, Fan Y, et al. To be,or not to be: NF-κB is the answer-role of Rel/ NF-κB in the regulation of apoptosis.[J] Oncogene 2003;22(56):8961-8982.
[24] Karin M, Cao Y, Greten FR,et al. NF-kappaB in cancer: from innocent bystander to major culprit.[J]. Nat Rev Cancer. 2002 ;2(4):301-310.
[25] Baldwin AS. Control of oncogenesis and cancer therapy resistance by the transcription factor NF-kappaB,[J]. Clin Invest. 2001 ;107(3):241-246.
[26] Davis RE,Brown KD, Siebenlist U et al. 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.
[27] Lam LT, Davis RE, Pierce J et al. Small molecule inhibitors of IkappaB kinase are selectively toxic for subgroups of diffuse large B-cell lymphoma defined by gene expression profiling.[J] Clin Cancer Res. 2005 ;11(1):28-40.
[28] Tzankov A, Pehrs AC, Zimpfer A et al. Prognostic significance of CD44 expression in diffuse large B cell lymphoma of activated and germinal centre B cell-like types: a tissue microarray analysis of 90 cases.[J] Clin Pathol. 2003 ;56(10):747-52.
[29] Bertin J,Wang L, Guo Y et al. CARD11 and CARD14 are novel caspase recruitment domain (CARD)/membrane-associated guanylate kinase (MAGUK) family members that interact with BCL10 and activate NF-kappa B.[J]. Biol Chem. 2001;276(15):11877-11882.
[30] Ngo VN, Davis RE, Lamy L et al. A loss-of-function RNA interference screen for molecular targets in cancer[J]. Nature. 2006 ;441(7089):106-110.
[31] Thome M. CARMA1, BCL-10 and MALT1 in lymphocyte development and activation[J]. Nat Rev Immunol. 2004 ;4(5):348-359.