Bruton Tyrosine Kinase (BTK) and Its Role in B-cell Malignancy

REFERENCES

• Bruton, O.C. (1952) Agammaglobulinemia. Pediatrics: 9;722–8.
   PubMed Web of Science ®Google Scholar
• Vetrie D, Vorechovský I, Sideras P, The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases. Nature. 1993;361:226–233.
   PubMed Web of Science ®Google Scholar
• Tsukada S, Saffran DC, Rawlings DJ Deficient expression of a B cell cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia. Cell 1993;72:279–290.
   Google Scholar
• Genevier HC, Hinshelwood S, Gaspar HB, Expression of Bruton's tyrosine kinase protein within the B cell lineage. Eur J Immunol. 1994;24:3100–3105.
   PubMed Web of Science ®Google Scholar
• Smith CI, Baskin B, Humire-Greiff P, Expression of Bruton's agammaglobulinemia tyrosine kinase gene, BTK, is selectively down-regulated in T lymphocytes and plasma cells. J Immunol. 1994;152:557–565.
   PubMed Web of Science ®Google Scholar
• de Weers M, Verschuren MCM, Kraakman MEM, The Bruton's tyrosine kinase gene is expressed throughout B cell differentiation, from early precursor B cell stages preceding immunoglobulin gene rearrangement up to mature B cell stages. Eur J. Immunol. 1993;23:3109–3114.
   PubMed Web of Science ®Google Scholar
• Conley ME, Dobbs AK, Farmer DM Primary B cell immunodeficiencies: comparisons and contrasts. Annu. Rev. Immunol. 2009;27:199–227.
   PubMed Web of Science ®Google Scholar
• Tsukada S, Rawlings DJ, Witte ON Role of Bruton's tyrosine kinase in immunodeficiency. Curr. Opin. Immunol. 1994;6:623–630.
   PubMed Web of Science ®Google Scholar
• Rawlings DJ, Saffran DC, Tsukada S, Mutation of unique region of Bruton's tyrosine kinase in immunodeficient XID mice. Science 1993;261:358–361.
   PubMed Web of Science ®Google Scholar
• Satterthwaite AB, Cheroutre H, Khan WN, Sideras P, Witte ON. Btk dosage determines sensitivity to B cell antigen receptor cross-linking. Proc Natl. Acad. Sci. U. S. A. 1997;94:13152–13157.
   PubMed Web of Science ®Google Scholar
• Kerner, JD, Appleby MW, Mohr RN, Impaired expansion of mouse B cell progenitors lacking Btk. Immunity. 1995;3:301–312.
   PubMed Web of Science ®Google Scholar
• Mohamed AJ, Nore BF, Christensson B, Smith CIE. Signaling of Bruton's tyrosine kinase, Btk. 1999; Scand J. Immunol 49:113–118.
   Google Scholar
• Li T, Rawlings DJ, Park H, Constitutive membrane association potentiates activation of Bruton tyrosine kinase. Oncogene 1997;15:1357–1383.
   Google Scholar
• Varnai P, Rother KI, and Balla T. Phosphatidylinositol 3-kinase-dependent membrane association of the Bruton's tyrosine kinase pleckstrin homology domain visualized in single living cells. J. Biol. Chem. 1999;274:10983–10989.
   PubMed Web of Science ®Google Scholar
• Humphries LA, Dangelmaier C, Sommer K Tec kinases mediate sustained calcium influx via site-specific tyrosine phosphorylation of the phospholipase C gamma Src homology 2-Src homology 3 linker. J Biol Chem. 2004;279:37651–37661.
   PubMed Web of Science ®Google Scholar
• Fluckiger AC, Li Z, Kato RM, Btk/Tec kinases regulate sustained increases in intracellular Ca2+ following B-cell receptor activation. EMBO J. 1998;17:1973–1985.
   PubMed Web of Science ®Google Scholar
• Jiang A, Craxton A, Kurosaki T, Clark EA. Different protein tyrosine kinases are required for B cell antigen receptor-mediated activation of extracellular signal-regulated kinase, c-Jun NH2-terminal kinase 1, and p38 mitogen-activated protein kinase. J. Exp Med. 1998;188:1297–1306.
   PubMed Web of Science ®Google Scholar
• Kurosaki T. Genetic analysis of B cell antigen receptor signaling. Annu Rev. Immunol. 1999;17:555–592.
   PubMed Web of Science ®Google Scholar
• Mao C, Zhou M, Uckun FM. Crystal structure of Bruton's tyrosine kinase domain suggests a novel pathway for activation and provides insights into the molecular basis of X-linked agammaglobulinemia. J. Biol Chem. 2001;276:41435–41443.
   PubMed Web of Science ®Google Scholar
• Marcotte DJ, Liu YT, Arduini RM, Structures of human Bruton's tyrosine kinase in active and inactive conformations suggest a mechanism of activation for TEC family kinases. Protein. Sci. 2010;19:429–439.
   PubMed Web of Science ®Google Scholar
• Kuglstatter A, Wong A, Tsing S, Insights into the conformational flexibility of Bruton's tyrosine kinase from multiple ligand complex structures. Protein Sci. 2011;20:428–436.
   PubMed Web of Science ®Google Scholar
• Niiro H, Clark EA Regulation of B-cell fate by antigen-receptor signals. Nat. Rev. Immunol. 2002;2:945–956.
   PubMed Web of Science ®Google Scholar
• Kraus, M., Alimzhanov, M. B., Rajewsky, N, Rajewsky, K. Survival of resting mature B lymphocytes depends on BCR signaling via the Igα/β heterodimer. Cell 2004;117:787–800.
   PubMed Web of Science ®Google Scholar
• 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.
   Google Scholar
• Gauld SB, Dal Porto JM, Cambier JC B cell antigen receptor signaling: roles in cell development and disease. Science 2002;296:1641–1642.
   PubMed Web of Science ®Google Scholar
• Afar DE, Park H, Howell BW Regulation of Btk by Src family tyrosine kinases. Mol. Cell. Biol. 1996;16:3465–3471.
   PubMed Web of Science ®Google Scholar
• Cheng G, Ye ZS, Baltimore D. Binding of Bruton's tyrosine kinase to Fyn, Lyn, or Hck through a Src homology 3 domain-mediated interaction. Proc Natl. Acad. Sci. USA. 1994;91:8152–8155.
   PubMed Web of Science ®Google Scholar
• Pereira S, Lowell C. (2003) The Lyn tyrosine kinase negatively regulates neutrophil integrin signaling. J Immunol. Aug 1;171(3):1319–27.
   Google Scholar
• Kawakami Y, Kitaura J, Satterthwaite AB, Redundant and opposing functions of two tyrosine kinases, Btk and Lyn, in mast cell activation. J Immunol. 2000;165:1210–9.
   PubMed Web of Science ®Google Scholar
• Srinivasan L, Sasaki Y, Calado DP, PI3 kinase signals BCR-dependent mature B cell survival. Cell. 2009;139:573–586.
   PubMed Web of Science ®Google Scholar
• Anderson JS, Teutsch M, Dong Z, Wortis HH. An essential role for Bruton's tyrosine kinase in the regulation of B-cell apoptosis. Proc. Natl. Acad. Sci USA. 1996;93:10966–10971.
   PubMed Web of Science ®Google Scholar
• Petro, JB, Rahman SM, Ballard DW, Khan WN. Bruton's tyrosine kinase is required for activation of IkB kinase and nuclear factor kB in response to B cell receptor engagement. J. Exp. Med. 2000;191:1745–1754.
   PubMed Web of Science ®Google Scholar
• Saijo K, Mecklenbrauker I, Santana A, Protein kinase C beta controls nuclear factor kappaB activation in B cells through selective regulation of the IkappaB kinase alpha. J. Exp. Med 2002;195:1647–1652.
   PubMed Web of Science ®Google Scholar
• Khan WN. Regulation of B lymphocyte development and activation by Bruton's tyrosine kinase. Immunol Res. 2001;23:147–56.
   PubMed Web of Science ®Google Scholar
• Yu L, Mohamed AJ, Simonson OE, Proteasome-dependent autoregulation of Bruton tyrosine kinase (Btk) promoter via NF-kappaB. Blood. 2008;111:4617–26.
   PubMed Web of Science ®Google Scholar
• Jongstra-Bilen J, Puig Cano A, Hasija M, Xiao H, Smith CI, Cybulsky MI: Dual functions of Bruton's tyrosine kinase and Tec kinase during Fcgamma receptor-induced signaling and phagocytosis. J. Immunol. 2008;181:288–298.
   PubMed Web of Science ®Google Scholar
• Nimmerjahn F, Ravetch JV. Fcγ receptors as regulators of immune responses. Nat Immunol. 2008;8:34–47.
   Google Scholar
• Chang BY, Huang MM, Francesco M, The Bruton tyrosine kinase inhibitor PCI-32765 ameliorates autoimmune arthritis by inhibition of multiple effector cells. Arthritis Res Ther. 2011;13:R115
   PubMed Web of Science ®Google Scholar
• Ortolano S, Hwang IY, Han SB, Kehrl JH. Roles for phosphoinositide 3-kinases, Bruton's tyrosine kinase, and Jun kinases in B lymphocyte chemotaxis and homing. Eur J Immunol. 2006;36:1285–1295.
   PubMed Web of Science ®Google Scholar
• de Gorter DJ, Beuling EA, Kersseboom R, Bruton's tyrosine kinase and phospholipase Cgamma2 mediate chemokine-controlled B cell migration and homing. Immunity. 2007;26:93–104.
   PubMed Web of Science ®Google Scholar
• Bajenoff M, Egen JG, Koo LY, Stromal cell networks regulate lymphocyte entry, migration, and territoriality in lymph nodes. Immunity. 2006;25:989–1001.
   PubMed Web of Science ®Google Scholar
• Kinashi T. Intracellular signaling controlling integrin activation in lymphocytes. Nature Rev Immunol. 2005;5:546–559.
   PubMed Web of Science ®Google Scholar
• Jiang Y, Ma W, Wan Y, Kozasa T, Hattori S, Huang XY. The G protein G alpha12 stimulates Bruton's tyrosine kinase and a rasGAP through a conserved PH/BM domain. Nature 1998;395:808–13.
   Google Scholar
• Lowry WE, Huang XY. G Protein beta gamma subunits act on the catalytic domain to stimulate Bruton's agammaglobulinemia tyrosine kinase. J Biol Chem. 2002;277:1488–92.
   Google Scholar
• Spaargaren M, Beuling EA, Rurup ML, The B cell antigen receptor controls integrin activity through Btk and PLCgamma2. J Exp Med. 2003;198:1539–1550.
   PubMed Web of Science ®Google Scholar
• Sochorová K, Horváth R, Rozková D, Litzman J, Bartunková J. Impaired Toll-like receptor 8-mediated IL-6 and TNF-alpha production in antigen-presenting cells from patients with X-linked agammaglobulinemia. Blood. 2007;109:2553–6.
   PubMed Web of Science ®Google Scholar
• Horwood NJ, Mahon T, McDaid JP, Bruton's tyrosine kinase is required for lipopolysaccharide-induced tumor necrosis factor alpha production. J Exp Med. 2003;197:1603–1611.
   PubMed Web of Science ®Google Scholar
• Liu X, Zhan Z, Li D, Intracellular MHC class II molecules promote TLR-triggered innate immune responses by maintaining activation of the kinase Btk. Nat Immunol. 2011;12:416–424.
   PubMed Web of Science ®Google Scholar
• Lee K, Xu S, Wong E, Tergaonkar V, Lam, K. Bruton's tyrosine kinase separately regulates NFkB p65RelA activation and cytokine interleukin (IL)-10/IL-12 production in TLR9-stimulated B cells. J. Biol. Chem. 2008;283:11189–11198.
   PubMed Web of Science ®Google Scholar
• Hasan M, Lopez-Herrera G, Blomberg EM, Defective Toll-like receptor 9-mediated cytokine production in B cells from Bruton's tyrosine kinase-deficient mice. Immunology 2007;123:239–249.
   Google Scholar
• Jahrsdorfer B, Muhlenhoff L, Blackwell SE, B-cell lymphomas differ in their responsiveness to CpG oligodeoxynucleotides. Clin Cancer Res. 2005;11:1490–1499.
   Google Scholar
• Decker T, Schneller F, Sparwasser T, Immunostimulatory CpG-oligonucleotides cause proliferation, cytokine production, and an immunogenic phenotype in chronic lymphocytic leukemia B cells. Blood 2000;95:999–1006.
   PubMed Web of Science ®Google Scholar
• James RG, Biechele TL, Conrad WH Bruton's tyrosine kinase revealed as a negative regulator of Wnt-beta-catenin signaling. Sci Signal 2009;2(72): ra25.
   Google Scholar
• Kawakami Y, Miura T, Bissonnette R, Bruton's tyrosine kinase regulates apoptosis and JNK/SAPK kinase activity. Proc Natl Acad Sci U S A. 1997;94:3938–42.
   PubMed Web of Science ®Google Scholar
• Matsuda T, Takahashi-Tezuka M, Fukada T, et al. Association and activation of Btk and Tec tyrosine kinases by gp130, a signal transducer of the interleukin-6 family of cytokines. Blood 1995;85:627–33.
   PubMed Web of Science ®Google Scholar
• Rajaiya J, Hatfield M, Nixon JC, Rawlings DJ, Webb CF. Bruton's tyrosine kinase regulates immunoglobulin promoter activation in association with the transcription factor Bright. Mol Cell Biol. 2005;25:2073–84.
   PubMed Web of Science ®Google Scholar
• Mukhopadhyay S, Mohanty M, Mangla A, Macrophage effector functions controlled by Bruton's tyrosine kinase are more crucial than the cytokine balance of T cell responses for microfilarial clearance. J. Immunol. 2002;168:2914–2921.
   PubMed Web of Science ®Google Scholar
• Mueller H, Stadtmann A, Van Aken H, Tyrosine kinase Btk regulates E-selectin-mediated integrin activation and neutrophil recruitment by controlling phopholipase C (PLC) γ2 and PI3Kγ pathways. Blood 2010;115:3118–3127.
   PubMed Web of Science ®Google Scholar
• Fiedler K, Sindrilaru A, Terszowski G, Neutrophil development and function critically depend on Bruton tyrosine kinase in a mouse model of X-linked agammaglobulinemia. Blood 2011;117:1329–1339.
   PubMed Web of Science ®Google Scholar
• Su Q, Zhou Y, Johns RA. Bruton's tyrosine kinase (Btk) is a binding partner for hypoxia induced mitogenic factor (HIMF/FIZZ1) and mediates myeloid cell chemotaxis. FASEB J. 2007;21:1376–1382.
   Google Scholar
• Mangla A, Khare A, Vineeth V Pleiotropic consequences of Bruton tyrosine kinase deficiency in myeloid lineages lead to poor inflammatory responses. Blood 2004;104:1191–1197.
   PubMed Web of Science ®Google Scholar
• Lee SH, Kim T, Jeong D, Kim N, Choi Y. The tec family tyrosine kinase Btk Regulates RANKL-induced osteoclast maturation. J Biol Chem. 2008;283:11526–11534.
   PubMed Web of Science ®Google Scholar
• Shinohara M, Koga T, Okamoto K, Tyrosine kinases Btk and Tec regulate osteoclast differentiation by linking RANK and ITAM signals. Cell 2008;132:794–806.
   PubMed Web of Science ®Google Scholar
• Danks L, Workman S, Webster D, Horwood NJ. Elevated cytokine production restores bone resorption by human Btk-deficient osteoclasts. J Bone Miner Res 2011;26:182–192.
   Google Scholar
• Gilfillan AM, Tkaczyk C. Integrated signalling pathways for mast-cell activation. Nat Rev Immunol. 2006;6:218–30.
   PubMed Web of Science ®Google Scholar
• Kawakami Y, Yao L, Miura T, Tsukada S, Witte O, Kawakami T. Tyrosine phosphorylation and activation of Bruton tyrosine kinase upon Fc epsilon RI cross-linking. Mol Cell Biol. 1994;14:5108–5113.
   PubMed Web of Science ®Google Scholar
• Hata BD, Kawakami Y, Inagaki N, Involvement of Bruton's tyrosine kinase in FcεRI-dependent mast cell degranulation and cytokine production. J Exp Med. 1998;187:1235–1247.
   PubMed Web of Science ®Google Scholar
• MacGlashan D Jr. IgE receptor and signal transduction in mast cells and basophils.Curr Opin Immunol. 2008;20:717–23.
   PubMed Web of Science ®Google Scholar
• Setoguchi R, Kinashi T, Sagara H, Hirosawa K, Takatsu K. Defective degranulation and calcium mobilization of bone-marrow derived mast cells from Xid and Btk-deficient mice. Immunol Lett. 1998;64:109–18.
   PubMed Web of Science ®Google Scholar
• Johansson A, Rudolfsson S, Hammarsten P, Mast cells are novel independent prognostic markers in prostate cancer and represent a target for therapy. Am J Pathol. 2010;177:1031–41.
   PubMed Web of Science ®Google Scholar
• Soucek L, Buggy JJ, Kortlever R, Modeling pharmacological inhibition of mast cell degranulation as a therapy for insulinoma. Neoplasia. 2011;13:1093–100.
   Google Scholar
• Liu J, Fitzgerald ME, Berndt MC, Jackson CW, Gartner TK. Bruton tyrosine kinase is essential for botrocetin/VWF-induced signaling and GPIb-dependent thrombus formation in vivo. Blood 2006;108:2596–2603.
   PubMed Web of Science ®Google Scholar
• Oda A, Ikeda Y, Ochs HD, Rapid tyrosine phosphorylation and activation of Bruton's tyrosine/Tec kinases in platelets induced by collagen binding of CD32 cross-linking. 2000; Blood 95:1663–1670.
   PubMed Web of Science ®Google Scholar
• Quek LS, Bolen J, Watson SP. A role for Bruton's tyrosine kinase (Btk) in platelet activation by collagen. Curr Biol. 1998;8:1137–1140.
   PubMed Web of Science ®Google Scholar
• van der Meer JW, Weening RS, Schellekens PT, van Munster IP, Nagengast FM. Colorectal cancer in patients with X-linked agammaglobulinaemia. Lancet 1993;341:1439–1440.
   PubMed Web of Science ®Google Scholar
• Brosens LA, Tytgat KM, Morsink FH, Multiple colorectal neoplasms in X-linked agammaglobulinemia. Clin. Gastroenterol. Hepatol. 2008;6:115–119.
   Google Scholar
• Middendorp S, Zijlstra AJ, Kersseboom R, Dingjan GM, Jumaa H, Hendriks RW. Tumor suppressor function of Bruton tyrosine kinase is independent of its catalytic activity. Blood. 2005;105:259– 65.
   PubMed Web of Science ®Google Scholar
• Mohamed AJ, Yu L, Bäckesjö CM, Bruton's tyrosine kinase (Btk): function, regulation, and transformation with special emphasis on the PH domain. Immunol Rev. 2009;228:58–73.
   PubMed Web of Science ®Google Scholar
• Meeker T, Lowder J, Cleary ML, Emergence of idiotype variants during treatment of B-cell lymphoma with anti-idiotype antibodies. N Engl J Med. 1985;312:1658–1665.
   PubMed Web of Science ®Google Scholar
• Kuppers R. Mechanisms of B-cell lymphoma pathogenesis. Nat Rev Cancer. 2005;5:251–262.
   PubMed Web of Science ®Google Scholar
• Gururajan M, Jennings CD, Bondada S. Cutting edge: constitutive B cell receptor signaling is critical for basal growth of B lymphoma. J. Immunol. 2006;176:5715–5719.
   PubMed Web of Science ®Google Scholar
• Irish JM, Czerwinski DK, Nolan GP, Levy R. Altered B-cell receptor signaling kinetics distinguish human follicular lymphoma B cells from tumor-infiltrating nonmalignant B cells. Blood 2006;108:3135–3142.
   PubMed Web of Science ®Google Scholar
• Lopez-Giral S, Quintana NE, Cabrerizo M, Chemokine receptors that mediate B cell homing to secondary lymphoid tissues are highly expressed in B cell chronic lymphocytic leukemia and non-Hodgkin lymphomas with widespread nodular dissemination. J Leukoc Biol. 2004;76:462–471.
   PubMed Web of Science ®Google Scholar
• Pals ST, de Gorter DJJ, Spaargaren M. Lymphoma dissemination: the other face of lymphocyte homing. Blood 2007;110:3102–3111.
   PubMed Web of Science ®Google Scholar
• Teicher BA, Fricker SP. CXCL12(SDF-1)/CXCR4 pathway in cancer. Clin Cancer Res. 2010;16:2927–2931.
   PubMed Web of Science ®Google Scholar
• Kurtova AV, Tamayo AT, Ford RD, Burger JA Mantle cell lymphoma cells express high levels of CXCR4, CXCR5, and VLA-4 (CD49d): importance for interactions with the stromal microenvironment and specific targeting. Blood. 2009;113:4604–4613.
   PubMed Web of Science ®Google Scholar
• Trentin L, Cabrelle A, Facco M, Homeostatic chemokines drive migration of malignant B cells in patients with non-Hodgkin lymphomas. Blood. 2004;104:502–508.
   PubMed Web of Science ®Google Scholar
• Kurtova AV, Tamayo AT, Ford RJ, Burger JA. Mantle cell lymphoma cells express high levels of CXCR4, CXCR5, and VLA-4 (CD49d): importance for interactions with the stromal microenvironment and specific targeting. Blood. 2009;113:4604–4613.
   PubMed Web of Science ®Google Scholar
• Quiroga MP, Balakrishnan K, Kurtova AV, B-cell antigen receptor signaling enhances chronic lymphocytic leukemia cell migration and survival: specific targeting with a novel spleen tyrosine kinase inhibitor, R406. Blood. 2009;114:1029–1037.
   PubMed Web of Science ®Google Scholar
• Burger JA, Quiroga MP, Hartmann E, High-level expression of the T cell chemokines CCL3 and CCL4 by chronic lymphocytic leukemia B cells in nurselike cell cocultures and after BCR stimulation. Blood. 2009;113:3050–3058.
   PubMed Web of Science ®Google Scholar
• Sanz-Rodriguez F, Hidalgo A, Teixido J. Chemokine stromal cell-derived factor-1 alpha modulates VLA-4 integrin-mediated multiple myeloma cell adhesion to CS-1/fibronectin and VCAM-1. Blood. 2001;97:346–351.
   PubMed Web of Science ®Google Scholar
• Corcione A, Arduino N, Ferretti E, CCL19 and CXCL12 trigger in vitro chemotaxis of human mantle cell lymphoma B cells. Clin Cancer Res; 2004: 10:964–971.
   PubMed Web of Science ®Google Scholar
• Lenz G, Wright G, Dave SS Stromal gene signatures in large-B-cell lymphomas. N Engl J Med. 2008;359:2313–2323.
   PubMed Web of Science ®Google Scholar
• Petit I, Jin D, Rafii S The SDF-1-CXCR4 signaling pathway: a molecular hub modulating neo-angiogenesis. Trends Immunol. 2007;28:299–307.
   PubMed Web of Science ®Google Scholar
• Mahajan S, Ghosh S, Sudbeck EA, Rational design and synthesis of a novel anti-leukemic agent targeting Bruton's tyrosine kinase (BTK), LFM-A13 [alpha-cyano-beta-hydroxy-beta-methyl-N-(2, 5-dibromophenyl)propenamide]. J Biol Chem. 1999;274:9587–99.
   PubMed Web of Science ®Google Scholar
• van den Akker E, van Dijk TB, Schmidt U, The Btk inhibitor LFM-A13 is a potent inhibitor of Jak2 kinase activity. Biol Chem 2004;385:409–13.
   PubMed Web of Science ®Google Scholar
• Uckun FM Chemosensitizing anti-cancer activity of LFM-A13, a leflunomide metabolite analog targeting polo-like kinases. Cell Cycle 2007:6;3021–6.
   PubMed Web of Science ®Google Scholar
• Hantschel O, Rix U, Schmidt U, The Btk tyrosine kinase is a major target of the Bcr-Abl inhibitor dasatinib. Proc Natl Acad Sci U S A. 2007; 104;13283–8.
   Google Scholar
• Honigberg L, Smith AM, Sirisawad M, 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 U S A. 2010;107:13075–80.
   PubMed Web of Science ®Google Scholar
• Pan Z, Scheerens H, Li SJ, Discovery of selective irreversible inhibitors for Bruton's tyrosine kinase. ChemMedChem 2007;2:58–61.
   PubMed Web of Science ®Google Scholar
• Advani RH, Sharman JP, Smith SM The Btk Inhibitor PCI-32765 Is Highly Active And Well Tolerated In Patients (Pts) With Relapsed/Refractory B Cell Malignancies: Final Results From A Phase I Study Ann Oncol 2011;22 (suppl 4): 153
   Google Scholar
• Evans, E, Tester, R, Aslanian S, Clinical Development of AVL-292; A Potent, Selective Covalent Btk Inhibitor for the Treatment of B Cell Malignancies. ASH Annual Meeting Abstracts. 2011;118: 3485
   Google Scholar
• MacGlashan D, Honigberg LA, Smith A, Buggy J, Schroeder JT Inhibition of IgE-mediated secretion from human basophils with a highly selective Bruton's tyrosine kinase, Btk, inhibitor. International Immunopharmacology 2011;11:475–479.
   PubMed Web of Science ®Google Scholar
• Davis RE, Ngo VN, Lenz G, Chronic active B-cell-receptor signaling in diffuse large B-cell lymphoma. Nature 2010;463:88–92.
   PubMed Web of Science ®Google Scholar
• Sabine P, Balasubramanian, S, Pham, LV Activity of Bruton's Tyrosine Kinase (Btk) Inhibitor PCI-32765 in Mantle Cell Lymphoma (MCL) Identifies Btk As a Novel Therapeutic Target ASH Annual Meeting Abstracts, 2011;118:3688
   Google Scholar
• Middendorp S, Dingjan GM, Maas A Function of Bruton's Tyrosine Kinase during B Cell Development Is Partially Independent of Its Catalytic Activity J Immunol. 2003;171:5988–5996.
   Google Scholar
• Chan AC, Iwashima M, Turck CW, Weiss A. ZAP-70: a 70 kd protein-tyrosine kinase that associates with the TCR zeta chain. Cell. 1992;71:649–662.
   PubMed Web of Science ®Google Scholar
• Wiestner A, Rosenwald A, Barry TS, ZAP-70 expression identifies a chronic lymphocytic leukemia subtype with unmutated immunoglobulin genes, inferior clinical outcome, and distinct gene expression profile. Blood. 2003;101:4944–4951.
   PubMed Web of Science ®Google Scholar
• Chen L. Apgar J, Huynh L, ZAP-70 directly enhances IgM signaling in chronic lymphocytic leukemia Blood. 2005;105:2036–2041.
   PubMed Web of Science ®Google Scholar
• Chiorazzi N, Ferrarini M. Cellular origin(s) of chronic lymphocytic leukemia: cautionary notes and additional considerations and possibilities Blood 2011;117:1781–91.
   PubMed Web of Science ®Google Scholar
• Corcos D, Osborn MJ, Matheson LS. B-cell receptors and heavy chain diseases: guilty by association? Blood. 2011;117:6991–8.
   Google Scholar
• O'Brien S, Burger JA, Blum K The Bruton's Tyrosine Kinase (BTK) Inhibitor PCI-32765 Induces Durable Responses in Relapsed or Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL): Follow-up of a Phase Ib/II Study ASH Annual Meeting Abstracts. 2011;118:983
   Google Scholar
• Chang, BY, Francesco, M, Magadala, Egress of CD19+CD5+ Cells Into Peripheral Blood Following Treatment with the Bruton Tyrosine Kinase Inhibitor, PCI-32765, in Mantle Cell Lymphoma Patients ASH Annual Meeting Abstracts. 2011, 118:954
   Google Scholar
• Herman SE, Gordon AL, Hertlein E, 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.
   PubMed Web of Science ®Google Scholar
• Ponader S, Chen SS, Buggy JJ, Bruton's tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo. Blood. Dec 16, 2011. [Epub ahead of print]
   PubMed Web of Science ®Google Scholar
• Alizadeh AA, Eisen MB, Davis RE, Distinct types of diffuse large B cell lymphoma identified by gene expression profiling. Nature 2000;403:503–511.
   PubMed Web of Science ®Google Scholar
• Staudt, LM, Dunleavy K, Buggy JJ, 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;118:2716
   Google Scholar
• Wang, L, Martin, P, Blum, KA, 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. ASH Annual Meeting Abstracts. 2011;118:442
   Google Scholar
• Pighi C, Gu TL, Dalai I, Phospho-proteomic analysis of mantle cell lymphoma cells suggests a pro-survival role of B-cell receptor signaling. Cell Oncol (Dordr). 2011;34:141–53.
   Google Scholar
• Psyrri A, Papageorgiou S, Liakata E, Phosphatidylinositol 3′-kinase catalytic subunit alpha gene amplification contributes to the pathogenesis of mantle cell lymphoma. Clin Cancer Res. 2009;15:5724–32.
   PubMed Web of Science ®Google Scholar
• Chauhan D, Li G, Auclair D, Identification of genes regulated by dexamethasone in multiple myeloma cells using oligonucleotide arrays. Oncogene 2002;21:1346–1358.
   PubMed Web of Science ®Google Scholar
• Tai, Y-T, Chang, BY, Kong, S-Y, Targeting Brouton's Tyrosine Kinase with PCI-32765 Blocks Growth and Survival of Multiple Myeloma and Waldenström Macroglobulinemia Via Potent Inhibition of Osteoclastogenesis, Cytokines/Chemokine Secretion, and Myeloma Stem-Like Cells in the Bone Marrow Microenvironment ASH Annual Meeting Abstracts. 2011;118:883
   Google Scholar
• Bam R, Pennisi A, Li X, Bruton's Tyrosine Kinase (Btk) Is Indispensable for Myeloma Cell Migration towards SDF-1 and Induction of Osteoclastogenesis and Osteolytic Bone Disease. ASH Annual Meeting Abstracts 2010;116:447.
   Google Scholar
• Matsui W, Huff CA, Wang O, Characterization of clonogenic multiple myeloma cells. Blood 2004;103:2332–2336.
   PubMed Web of Science ®Google Scholar
• Bam R, Ling W, Khan S, Cell Surface CXCR4 and BTK Expression Are Associated in Myeloma Cells and Osteoclast Precursors and Mediate Myeloma Cell Homing and Clonogenicity, and Osteoclastogenesis ASH Annual Meeting Abstracts. 2011;118:884
   Google Scholar
• Feldhahn N, Río P, Soh BN, Deficiency of Bruton's tyrosine kinase in B cell precursor leukemia cells. Proc Natl Acad Sci U S A. 2005;102:13266–71.
   PubMed Web of Science ®Google Scholar
• Feldhahn N, Klein F, Mooster JL, Mimicry of a constitutively active pre-B cell receptor in acute lymphoblastic leukemia cells J Exp Med. 2005;201:1837–52.
   PubMed Web of Science ®Google Scholar
• Jongstra-Bilen J, Puig Cano A, Hasija M, Xiao H, Smith CI, Cybulsky MI: Dual functions of Bruton's tyrosine kinase and Tec kinase during Fcgamma receptor-induced signaling and phagocytosis. J Immunol 2008, 181:288–298.
   PubMed Web of Science ®Google Scholar
• Nimmerjahn F, Ravetch JV (2008). Fcγ receptors as regulators of immune responses. Nat Immunol 8:34–47.
   Google Scholar
• Sochorová K, Horváth R, Rozková D, Litzman J, Bartunková J (2007). Impaired Toll-like receptor 8-mediated IL-6 and TNF-alpha production in antigen-presenting cells from patients with X-linked agammaglobulinemia. Blood 109:2553–6.
   PubMed Web of Science ®Google Scholar