B‐cell receptor signalling and its crosstalk with other pathways in normal and malignant cells

European Journal of Haematology - Tập 94 Số 3 - Trang 193-205 - 2015
Václav Šeda1, Marek Mráz1,2,3
1Central European Institute of Technology, Masaryk University, Brno, Czech Republic
2Department of Internal Medicine, Hematology and Oncology, University Hospital Brno
3Faculty of Medicine, Masaryk University, Brno, Czech Republic

Tóm tắt

Abstract

The physiology of B cells is intimately connected with the function of their B‐cell receptor (BCR). B‐cell lymphomas frequently (dys)regulate BCR signalling and thus take advantage of this pre‐existing pathway for B‐cell proliferation and survival. This has recently been underscored by clinical trials demonstrating that small molecules (fosfamatinib, ibrutinib, idelalisib) inhibiting BCR‐associated kinases (SYK, BTK, PI3K) have an encouraging clinical effect. Here we describe the current knowledge of the specific aspects of BCR signalling in diffuse large B‐cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic leukaemia (CLL) and normal B cells. Multiple factors can contribute to BCR pathway (dys)regulation in these malignancies and the activation of ‘chronic’ or ‘tonic’ BCR signalling. In lymphoma B cells, the balance of initiation, amplitude and duration of BCR activation can be influenced by a specific immunoglobulin structure, the expression and mutations of adaptor molecules (like GAB1, BLNK, GRB2, CARD11), the activity of kinases (like LYN, SYK, PI3K) or phosphatases (like SHIP‐1, SHP‐1 and PTEN) and levels of microRNAs. We also discuss the crosstalk of BCR with other signalling pathways (NF‐κB, adhesion through integrins, migration and chemokine signalling) to emphasise that the ‘BCR inhibitors’ target multiple pathways interconnected with BCR, which might explain some of their clinical activity.

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Tài liệu tham khảo

10.1016/B978-0-12-800267-4.00004-3

10.1016/j.molimm.2004.04.008

10.1038/nri1808

10.1126/science.8332901

10.1016/j.coi.2004.03.014

10.1016/S1074-7613(00)00079-0

10.1038/nri801

10.1074/jbc.274.43.30644

10.1146/annurev.iy.12.040194.002325

10.1007/978-0-387-79311-5_5

10.1111/j.1600-065X.2008.00748.x

10.1016/0092-8674(95)90171-X

10.1128/MCB.14.11.7306

Pao LI, 1997, Syk, but not Lyn, recruitment to B cell antigen receptor and activation following stimulation of CD45‐ B cells, J Immunol, 158, 2663, 10.4049/jimmunol.158.6.2663

10.1016/S0968-0004(02)02166-7

10.1084/jem.191.9.1545

10.1016/S0167-5699(97)80025-4

10.1046/j.1365-3083.2001.00868.x

10.1016/j.immuni.2010.06.006

10.1016/j.immuni.2009.12.005

10.1016/j.coi.2010.03.009

10.1016/S0092-8674(00)80373-6

10.1016/j.cell.2009.08.041

10.1016/0165-2478(94)00196-X

10.1038/ni.1749

10.1038/29802

10.1073/pnas.93.15.7865

10.1073/pnas.1732008100

10.1038/nature08638

10.1038/nature11309

10.1056/NEJMra0807082

10.1038/nrc1589

10.1084/jem.20062041

10.1038/ni.1764

10.1126/science.1076963

10.1084/jem.20061923

10.1038/ni752

10.1056/NEJMoa012914

10.1126/science.1153629

10.1038/nature04687

10.1182/blood.V94.6.1848

10.1182/blood-2006-03-012948

10.1172/JCI19399

10.1182/blood-2011-03-343434

10.1172/JCI24387

10.2119/2008-00102.Catera

10.1182/blood-2008-06-162024

10.1182/blood-2007-11-125450

10.1371/journal.pone.0015992

10.1084/jem.20121801

10.1371/journal.pone.0065203

10.1056/NEJMoa1109016

10.1038/nature10113

Blix ES, 2012, Altered BCR and CD40 signalling are associated with clinical outcome in small lymphocytic lymphoma/chronic lymphocytic leukaemia and marginal zone lymphoma patients, Br J Haematol, 159, 604

10.1371/journal.pone.0079987

10.1182/blood-2013-09-527234

10.3109/10428194.2013.796055

10.1182/blood-2014-03-559690

10.1182/blood-2006-05-026203

10.1158/1078-0432.CCR-05-0637

10.1111/j.1365-2141.2005.05883.x

10.1172/JCI61272

10.1016/S1097-2765(02)00739-6

10.1084/jem.20060221

10.4049/jimmunol.166.3.1507

10.4049/jimmunol.0803941

10.1038/ni1256

10.1016/S1074-7613(04)00381-4

10.1111/j.1600-065X.2010.00936.x

10.1172/JCI200522094

10.1182/blood-2013-02-485540

10.1038/nature09671

10.1038/nature09121

10.1182/blood-2007-04-087734

10.1182/blood.V93.6.1809.406k35_1809_1816

10.1016/S0962-8924(03)00002-3

10.1083/jcb.149.7.1419

10.1074/jbc.273.46.30630

10.1016/j.imlet.2005.11.017

10.1074/jbc.M010590200

10.1016/j.immuni.2013.02.021

10.1016/S0955-0674(97)80064-6

10.1038/sj.leu.2404138

10.1016/j.beha.2007.04.001

10.1182/blood-2002-10-3306

10.1182/blood-2004-05-1715

10.1056/NEJMoa040857

10.1182/blood-2006-12-062265

10.1016/1074-7613(95)90029-2

10.1084/jem.189.7.1163

10.1074/jbc.271.37.22782

10.1093/emboj/20.24.7085

10.1016/S0960-9822(99)80090-6

10.1074/jbc.273.52.35273

10.1196/annals.1381.021

10.1038/nrc3702

10.1097/CCO.0b013e3283589950

10.1158/2159-8290.CD-11-0249

10.1056/NEJMoa1215637

10.1002/eji.1830231210

10.1016/j.immuni.2006.11.012

10.1016/j.immuni.2004.07.012

10.1182/blood-2002-12-3945

10.1016/j.it.2003.12.003

10.1182/blood-2011-10-386417

10.1182/blood-2009-06-225326

Cariappa A, 1999, Accelerated emigration of B lymphocytes in the Xid mouse, J Immunol, 162, 4417, 10.4049/jimmunol.162.8.4417

10.1084/jem.20011866

10.1038/ni1100

10.1038/35018581

10.1016/S1074-7613(00)80131-4

10.1084/jem.193.6.755

10.1016/S1074-7613(00)80046-1

10.1038/382635a0

10.1084/jem.20041185

10.1084/jem.20020201

10.1002/humu.9321

10.1084/jem.192.11.1611

10.1002/j.1460-2075.1996.tb00867.x

10.1016/1074-7613(95)90114-0

10.4049/jimmunol.168.6.2695

Nomura K, 2000, Genetic defect in human X‐linked agammaglobulinemia impedes a maturational evolution of pro‐B cells into a later stage of pre‐B cells in the B‐cell differentiation pathway, Blood, 96, 610

10.1038/sj.emboj.7600944

10.1111/j.1365-2141.2011.08794.x

10.1182/asheducation-2011.1.96

10.1182/blood-2008-10-185827

10.1146/annurev.immunol.22.012703.104743

10.1182/blood-2013-06-507947

10.1172/JCI24176

10.1182/blood-2013-09-527853

10.1056/NEJMoa1400376

10.1056/NEJMoa1315226

10.1182/blood-2011-05-352492

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European Journal of Haematology

Tập 94 Số 3

193-205

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