Breaking good: The inexorable rise of BTK inhibitors in the treatment of chronic lymphocytic leukaemia

British Journal of Haematology

Volumn 166, Issue 1, 2014, Pages 12-22

  Hutchinson, Claire V ^a   Dyer, Martin J S ^a  

^a UNIVERSITY OF LEICESTER   (United Kingdom)

Author keywords

B cell receptor signalling; Bruton tyrosine kinase; Chronic lymphocytic leukaemia; Ibrutinib

Indexed keywords

ANTINEOPLASTIC AGENT; AVL 292; BRUTON TYROSINE KINASE; BRUTON TYROSINE KINASE INHIBITOR; CC 292; CGI 1746; CHLORAMBUCIL; GDC 0834; HM 71224; IBRUTINIB; LENALIDOMIDE; OFATUMUMAB; ONO 4059; RITUXIMAB; UNCLASSIFIED DRUG;

ANEMIA; ARTICLE; CANCER GROWTH; CANCER REGRESSION; CHRONIC LYMPHATIC LEUKEMIA; DIARRHEA; DRUG COST; DRUG EFFICACY; DRUG MECHANISM; DRUG TOLERABILITY; DRUG WITHDRAWAL; FATIGUE; HIGH RISK PATIENT; HUMAN; INFECTION; LYMPHOCYTOSIS; NAUSEA; NEUTROPENIA; OUTCOME ASSESSMENT; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PNEUMONIA; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROTEIN FUNCTION; PROTEIN TARGETING; RANDOMIZED CONTROLLED TRIAL (TOPIC); THROMBOCYTOPENIA; TREATMENT DURATION; TREATMENT INDICATION; TREATMENT RESPONSE;

B CELL RECEPTOR SIGNALLING; BRUTON TYROSINE KINASE; CHRONIC LYMPHOCYTIC LEUKAEMIA; IBRUTINIB;

ANTINEOPLASTIC AGENTS; CLINICAL TRIALS AS TOPIC; HUMANS; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; MOLECULAR TARGETED THERAPY; PROTEIN KINASE INHIBITORS; PROTEIN-TYROSINE KINASES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84902343396     PISSN: 00071048     EISSN: 13652141     Source Type: Journal    
DOI: 10.1111/bjh.12895     Document Type: Article

References (75)

1. Apollonio, B., Scielzo, C., Bertilaccio, M.T., Ten Hacken, E., Scarfo, L., Ranghetti, P., Stevenson, F., Packham, G., Ghia, P., Muzio, M. & Caligaris-Cappio, F. (2013) Targeting B-cell anergy in chronic lymphocytic leukemia. Blood, 121, S3871-S3878.
2. Barrientos, J.C., Barr, P.M., Flinn, I., Burger, J.A., Salman, Z., Clow, F., James, D.F., Graef, T., Friedberg, J.W., Rai, K.R. & O'Brien, S. (2013) Ibrutinib in combination with bendamustine and rituximab is active and tolerable in patients with relapsed/refractory CLL/SLL: final results of a Phase 1b study. Blood, 122, 525.
3. Bruton, O.C. (1952) Agammaglobulinemia. Pediatrics, 9, 722-728.
4. Burger, J.A. & Chiorazzi, N. (2013) B cell receptor signaling in chronic lymphocytic leukemia. Trends in Immunology, 4, 592-601.
5. Burger, J.A., Keating, M.J., Wierda, W.G., Hoellenriegel, J., Ferrajoli, A., Faderl, S., Lerner, S., Zacharian, G., Huang, X., James, D.F., Buggy, J.J., Kantarjian, H.M. & O'Brien, S.M. (2012) The Btk inhibitor ibrutinib (PCI-32765) in combination with rituximab is well tolerated and displays profound activity in high-risk chronic lymphocytic leukemia (CLL) patients. Blood (ASH Annual Meeting Abstracts), 120, 187.
6. Byrd, J.C., O'Brien, S. & James, D.F. (2013a) Ibrutinib in relapsed chronic lymphocytic leukemia. The New England Journal of Medicine, 369, 1278-1279.
7. Byrd, J.C., Furman, R.R., Coutre, S.E., Flinn, I.W., Burger, J.A., Blum, K.A., Grant, B., Sharman, J.P., Coleman, M., Wierda, W.G., Jones, J.A., Zhao, W., Heerema, N.A., Johnson, A.J., Sukbuntherng, J., Chang, B.Y., Clow, F., Hedrick, E., Buggy, J.J., James, D.F. & O'Brien, S. (2013b) Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. The New England Journal of Medicine, 369, 32-42.
8. Byrne, J.C., Ni Gabhann, J., Stacey, K.B., Coffey, B.M., McCarthy, E., Thomas, W. & Jefferies, C.A. (2013) Bruton's tyrosine kinase is required for apoptotic cell uptake via regulating the phosphorylation and localization of calreticulin. Journal of Immunology, 190, 5207-5215.
9. Davis, R.E., Ngo, V.N., Lenz, G., Tolar, P., Young, R.M., Romesser, P.B., Kohlhammer, H., Lamy, L., Zhao, H., Yang, Y., Xu, W., Shaffer, A.L., Wright, G., Xiao, W., Powell, J., Jiang, J.K., Thomas, C.J., Rosenwald, A., Ott, G., Muller-Hermelink, H.K., Gascoyne, R.D., Connors, J.M., Johnson, N.A., Rimsza, L.M., Campo, E., Jaffe, E.S., Wilson, W.H., Delabie, J., Smeland, E.B., Fisher, R.I., Braziel, R.M., Tubbs, R.R., Cook, J.R., Weisenburger, D.D., Chan, W.C., Pierce, S.K. & Staudt, L.M. (2010) Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature, 463, 88-92.
10. Di Paolo, J.A., Huang, T., Balazs, M., Barbosa, J., Barck, K.H., Bravo, B.J., Carano, R.A., Darrow, J., Davies, D.R., DeForge, L.E., Diehl, L., Ferrando, R., Gallion, S.L., Giannetti, A.M., Gribling, P., Hurez, V., Hymowitz, S.G., Jones, R., Kropf, J.E., Lee, W.P., Maciejewski, P.M., Mitchell, S.A., Rong, H., Staker, B.L., Whitney, J.A., Yeh, S., Young, W.B., Yu, C., Zhang, J., Reif, K. & Currie, K.S. (2011) Specific Btk inhibition suppresses B cell- and myeloid cell-mediated arthritis. Nature Chemical Biology, 7, 41-50.
11. Dolgin, E. (2013) Cancer's true breakthroughs. Nature Medicine, 19, 660-663.
12. Dubovsky, J.A., Beckwith, K.A., Natarajan, G., Woyach, J.A., Jaglowski, S., Zhong, Y., Hessler, J.D., Liu, T.M., Chang, B.Y., Larkin, K.M., Stefanovski, M.R., Chappell, D.L., Frissora, F.W., Smith, L.L., Smucker, K.A., Flynn, J.M., Jones, J.A., Andritsos, L.A., Maddocks, K., Lehman, A.M., Furman, R., Sharman, J., Mishra, A., Caligiuri, M.A., Satoskar, A.R., Buggy, J.J., Muthusamy, N., Johnson, A.J. & Byrd, J.C. (2013) Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1 selective pressure in T-lymphocytes. Blood, 122, 2539-2549.
13. Duhren-von Minden, M., Ubelhart, R., Schneider, D., Wossning, T., Bach, M.P., Buchner, M., Hofmann, D., Surova, E., Follo, M., Kohler, F., Wardemann, H., Zirlik, K., Veelken, H. & Jumaa, H. (2012) Chronic lymphocytic leukaemia is driven by antigen-independent cell-autonomous signalling. Nature, 489, 309-312.
14. Dyer, M.J., Vogler, M., Samuel, J., Jayne, S., Wagner, S., Pritchard, C. & Macip, S. (2013) Precision medicines for B-cell leukaemias and lymphomas; progress and potential pitfalls. British Journal of Haematology, 160, 725-733.
15. Eifert, C., Wang, X., Kokabee, L., Kourtidis, A., Jain, R., Gerdes, M.J. & Conklin, D.S. (2013) A novel isoform of the B cell tyrosine kinase BTK protects breast cancer cells from apoptosis. Genes, Chromosomes & Cancer, 52, 961-975.
16. von Eschenbach, A.C. (2006) Progress with a purpose: eliminating suffering and death due to cancer. Oncology (Williston Park), 20, 1691-1696.
17. Farooqui, M., Lozier, J.N., Valdez, J., Saba, N., Wells, A., Soto, S., Liu, D., Aue, G. & Wiestner, A. (2012) Ibrutinib (PCI 32765) rapidly improves platelet counts in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) patients and has minimal effects on platelet aggregation. Blood (ASH Annual Meeting Abstracts), 120, 1789.
18. Farooqui, M., Jones, J., Valdez, J., Martyr, S.E., Soto, S., Stetler-Stevenson, M., Yuan, C. & Wiestner, A. (2013) In patients with chronic lymphocytic leukemia (CLL) ibrutinib effectively reduces clonal IgM paraproteins and serum free light chains while increasing normal IgM, IgA serum levels, suggesting a nascent recovery of humoral immunity. Blood, 122, 4182.
19. Fischer, K., Bahlo, J., Fink, A.-M., Busch, R., Bottcher, S., Mayer, J., Dreger, P., Maurer, C., Engelke, A., Kneba, M., Dohner, H., Eichhorst, B.F., Wendtner, C.-M., Stilgenbauer, S. & Hallek, M. (2012) Extended follow up of the CLL8 protocol, a randomized phase-III trial of the German CLL Study Group (GCLLSG) comparing fludarabine and cyclophosphamide (FC) to FC plus rituximab (FCR) for previously untreated patients with chronic lymphocytic leukemia (CLL): results on survival, progression-free survival, delayed neutropenias and secondary malignancies confirm superiority of the FCR regimen. Blood (ASH Annual Meeting Abstracts), 120, 435.
20. Garg, N., Komarova, N.L., Benjamini, O., Keating, M.J., Wierda, W.G., Kantarjian, H.M., James, D.F., O'Brien, S.M. & Burger, J.A. (2013) Kinetics of chronic lymphocytic leukemia cells in tissues and blood during therapy with the BTK inhibitor ibrutinib. Blood, 122, 4166.
21. Genevier, H.C., Hinshelwood, S., Gaspar, H.B., Rigley, K.P., Brown, D., Saeland, S., Rousset, F., Levinsky, R.J., Callard, R.E., Kinnon, C. & Lovering R.C. (1994) Expression of Bruton's tyrosine kinase protein within the B cell lineage. European Journal of Immunology, 24, 3100-3105.
22. Goede, V., Fischer, K., Busch, R., Engelke, A., Eichhorst, B., Wendtner, C.M., Chagorova, T., de la Serna, J., Dilhuydy, M.S., Illmer, T., Opat, S., Owen, C.J., Samoylova, O., Kreuzer, K.A., Stilgenbauer, S., Dohner, H., Langerak, A.W., Ritgen, M., Kneba, M., Asikanius, E., Humphrey, K., Wenger, M. & Hallek, M. (2014) Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. The New England Journal of Medicine, 370, 1101-1110.
23. Goldacre, B. (2012) Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients. Fourth Estate, London.
24. de Gorter, D.J., Beuling, E.A., Kersseboom, R., Middendorp, S., van Gils, J.M., Hendriks, R.W., Pals, S.T. & Spaargaren, M. (2007) Bruton's tyrosine kinase and phospholipase Cgamma2 mediate chemokine-controlled B cell migration and homing. Immunity, 26, 93-104.
25. Gowans, J.L. & Knight, E.J. (1964) The route of re-circulation of lymphocytes in the rat. Proceedings of the Royal Society of London. Series B: Biological Sciences, 159, 257-282.
26. Harb, W.A., Hill, B.T., Gabrilove, J., Sharman, J.P., Schreeder, M.T., Barr, P.M., Foran, J.M., Miller, T.P., Burger, J.A., Kelly, K.R., Mahadevan, D., Ma, S., Barnett, E., Marine, J., Nava-Parada, P., Azaryan, A., Mei, J. & Kipps, T.J. (2013) Phase 1 study of single agent CC-292, a highly selective Bruton's tyrosine kinase (BTK) inhibitor, in relapsed/refractory chronic lymphocytic leukemia (CLL). Blood (ASH Annual Meeting Abstracts), 122, 1630.
27. Honda, F., Kano, H., Kanegane, H., Nonoyama, S., Kim, E.S., Lee, S.K., Takagi, M., Mizutani, S. & Morio, T. (2012) The kinase Btk negatively regulates the production of reactive oxygen species and stimulation-induced apoptosis in human neutrophils. Nature Immunology, 13, 369-378.
28. Honigberg, L.A., Smith, A.M., Sirisawad, M., Verner, E., Loury, D., Chang, B., Li, S., Pan, Z., Thamm, D.H., Miller, R.A. & Buggy, J.J. (2010) The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Proceedings of the National Academy of Sciences of the United States of America, 107, 13075-13080.
29. Hsu, J., Gu, Y., Tan, S.L., Narula, S., DeMartino, J.A. & Liao, C. (2013) Bruton's tyrosine kinase mediates platelet receptor-induced generation of microparticles: a potential mechanism for amplification of inflammatory responses in rheumatoid arthritis synovial joints. Immunology Letters, 150, 97-104.
30. Huck, K., Feyen, O., Niehues, T., Ruschendorf, F., Hubner, N., Laws, H.J., Telieps, T., Knapp, S., Wacker, H.H., Meindl, A., Jumaa, H. & Borkhardt, A. (2009) Girls homozygous for an IL-2-inducible T cell kinase mutation that leads to protein deficiency develop fatal EBV-associated lymphoproliferation. The Journal of Clinical Investigation, 119, 1350-1358.
31. Jaglowski, S.A., Jones, J.A., Flynn, J.M., Andritsos, L.A., Maddocks, K.J., Blum, K.A., Grever, M.R., Geyer, S.M., Woyach, J.A., Johnson, A.J., Heerema, N.A., Molnar, E., Stefanos, M., Devlin, S., Navarro, T., James, D.F., Lowe, A.M., Hedrick, E. & Byrd, J.C. (2012) A phase Ib/II study evaluating activity and tolerability of BTK inhibitor PCI-32765 and ofatumumab in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and related diseases. Journal of Clinical Oncology, 30(Suppl), abstr 6508.
32. Jiang, Y., Ma, W., Wan, Y., Kozasa, T., Hattori, S. & Huang, X.Y. (1998) The G protein G alpha12 stimulates Bruton's tyrosine kinase and a rasGAP through a conserved PH/BM domain. Nature, 395, 808-813.
33. Kantarjian, H.M., Fojo, T., Mathisen, M. & Zwelling, L.A. (2013) Cancer drugs in the United States: justum pretium-the just price. Journal of Clinical Oncology, 31, 3600-3604.
34. Keating, M.J., Tam, C.S., Wierda, W.G., O'Brien, S., Thomas, D.A., Cortes, J.E., Lerner, S. & Plunkett, W. (2012) Is chronic lymphocytic leukemia still incurable? Blood (ASH Annual Meeting Abstracts), 120, 3929.
35. Keating, M.J., Wierda, W.G., Hoellenriegel, J., Jeyakumar, G., Ferrajoli, A., Faderl, S.H., Cardenas-Turanzas, M., Lerner, S., Zacharian, G., Huang, X., Kantarjian, H.M. & O'Brien, S. (2013) Ibrutinib in combination with rituximab (iR) is well tolerated and induces a high rate of durable remissions in patients with high-risk chronic lymphocytic leukemia (CLL): new, updated results of a phase II trial In 40 patients. Blood, 122, 675.
36. Kim, E., Koehrer, S., Rosin, N.Y., Thomas, D.A., Ravandi, F., Kornblau, S.M., Kantarjian, H.M., O'Brien, S., Estrov, Z., Buggy, J.J. & Burger, J.A. (2012) Activity of Bruton's tyrosine kinase (BTK) inhibitor ibrutinib (PCI-32765) in B-cell acute lymphoblastic leukemia (B-ALL). Blood (ASH Annual Meeting Abstracts), 120, 2569.
37. King, L.B. & Freedman, B.D. (2009) B-lymphocyte calcium influx. Immunological Reviews, 231, 265-277.
38. Kozaki, R., Hutchinson, C., Jayne, S. & Dyer, M. (2013) The BTK-specific inhibitor ONO-4059 synergizes with the BCL2 inhibitor ABT-263. Haematologica, 98(s1), abstr P988.
39. Kraus, M., Alimzhanov, M.B., Rajewsky, N. & Rajewsky, K. (2004) Survival of resting mature B lymphocytes depends on BCR signaling via the Igalpha/beta heterodimer. Cell, 117, 787-800.
40. Kuglstatter, A., Wong, A., Tsing, S., Lee, S.W., Lou, Y., Villasenor, A.G., Bradshaw, J.M., Shaw, D., Barnett, J.W. & Browner, M.F. (2011) Insights into the conformational flexibility of Bruton's tyrosine kinase from multiple ligand complex structures. Protein Science, 20, 428-436.
41. Liu, L., Halladay, J.S., Shin, Y., Wong, S., Coraggio, M., La, H., Baumgardner, M., Le, H., Gopaul, S., Boggs, J., Kuebler, P., Davis, J.C. Jr, Liao, X.C., Lubach, J.W., Deese, A., Sowell, C.G., Currie, K.S., Young, W.B., Khojasteh, S.C., Hop, C.E. & Wong, H. (2011) Significant species difference in amide hydrolysis of GDC-0834, a novel potent and selective Bruton's tyrosine kinase inhibitor. Drug Metabolism and Disposition, 39, 1840-1849.
42. Lowry, W.E. & Huang, X.Y. (2002) G Protein beta gamma subunits act on the catalytic domain to stimulate Bruton's agammaglobulinemia tyrosine kinase. The Journal of Biological Chemistry, 277, 1488-1492.
43. Macias-Perez, I.M. & Flinn, I.W. (2013) GS-1101: a delta-specific PI3K inhibitor in chronic lymphocytic leukemia. Current Hematologic Malignancy Reports, 8, 22-27.
44. Mao, C., Zhou, M. & Uckun, F.M. (2001) 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. The Journal of Biological Chemistry, 276, 41435-41443.
45. Marcotte, D.J., Liu, Y.T., Arduini, R.M., Hession, C.A., Miatkowski, K., Wildes, C.P., Cullen, P.F., Hong, V., Hopkins, B.T., Mertsching, E., Jenkins, T.J., Romanowski, M.J., Baker, D.P. & Silvian, L.F. (2010) Structures of human Bruton's tyrosine kinase in active and inactive conformations suggest a mechanism of activation for TEC family kinases. Protein Science, 19, 429-439.
46. McLean, L.R., Zhang, Y., Zaidi, N., Bi, X., Wang, R., Dharanipragada, R., Jurcak, J.G., Gillespy, T.A., Zhao, Z., Musick, K.Y., Choi, Y.M., Barrague, M., Peppard, J., Smicker, M., Duguid, M., Parkar, A., Fordham, J. & Kominos, D. (2012) X-ray crystallographic structure-based design of selective thienopyrazole inhibitors for interleukin-2-inducible tyrosine kinase. Bioorganic & Medicinal Chemistry Letters, 22, 3296-3300.
47. O'Brien, S., Furman, R.R., Coutre, S.E., Sharman, J.P., Burger, J.A., Blum, K.A., Grant, B., Richards, D.A., Coleman, M., Wierda, W.G., Jones, J.A., Zhao, W., Heerema, N.A., Johnson, A.J., Izumi, R., Hamdy, A., Chang, B.Y., Graef, T., Clow, F., Buggy, J.J., James, D.F. & Byrd, J.C. (2014) Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2 trial. Lancet Oncology, 15, 48-58.
48. Ortolano, S., Hwang, I.Y., Han, S.B. & Kehrl, J.H. (2006) Roles for phosphoinositide 3-kinases, Bruton's tyrosine kinase, and Jun kinases in B lymphocyte chemotaxis and homing. European Journal of Immunology, 36, 1285-1295.
49. Pan, Z., Scheerens, H., Li, S.J., Schultz, B.E., Sprengeler, P.A., Burrill, L.C., Mendonca, R.V., Sweeney, M.D., Scott, K.C., Grothaus, P.G., Jeffery, D.A., Spoerke, J.M., Honigberg, L.A., Young, P.R., Dalrymple, S.A. & Palmer, J.T. (2007) Discovery of selective irreversible inhibitors for Bruton's tyrosine kinase. ChemMedChem, 2, 58-61.
50. Pechloff, K., Holch, J., Ferch, U., Schweneker, M., Brunner, K., Kremer, M., Sparwasser, T., Quintanilla-Martinez, L., Zimber-Strobl, U., Streubel, B., Gewies, A., Peschel, C. & Ruland, J. (2010) The fusion kinase ITK-SYK mimics a T cell receptor signal and drives oncogenesis in conditional mouse models of peripheral T cell lymphoma. The Journal of Experimental Medicine, 207, 1031-1044.
51. Qiu, Y. & Kung, H.J. (2000) Signaling network of the Btk family kinases. Oncogene, 19, 5651-5661.
52. Rizos, H., Menzies, A.M., Pupo, G.M., Carlino, M.S., Fung, C., Hyman, J., Haydu, L.E., Mijatov, B., Becker, T.M., Boyd, S.C., Howle, J., Robyn, S., Thompson, J.F., Kefford, R.F., Scolyer, R.A. & Long, G.V. (2014) BRAF inhibitor resistance mechanisms in metastatic melanoma; spectrum and clinical impact. Clinical Cancer Research, 20, 1965-1977.
53. Rule, S., Shah, N., Salles, G.A., Karlin, L., Morschhauser, F., Terriou, L., Dyer, M.J., Hutchinson, C., Fegan, C., Cartron, G., Knurowski, T., Wright, J.G., Saunders, A.J., Honda, H., Mazur, A., Yoshizawa, T., Kawabata, K. & Birkett, J.T. (2013) A phase I study of the oral btk inhibitor ONO-4059 in patients with relapsed/refractory B-cell lymphoma. Blood (ASH Annual Meeting Abstracts), 122, 4397.
54. Rushworth, S.A., MacEwan, D.J. & Bowles, K.M. (2013) Ibrutinib in relapsed chronic lymphocytic leukemia. The New England Journal of Medicine, 369, 1277-1278.
55. Rushworth, S.A., Murray, M.Y., Zaitseva, L., Bowles, K.M. & Macewan, D.J. (2014) Identification of Bruton's tyrosine kinase as a therapeutic target in acute myeloid leukemia. Blood, 123, 1229-1238.
56. Salles, G.A., Karlin, L., Rule, S., Shah, N., Morschhauser, F., Terriou, L., Dyer, M.J., Hutchinson, C.V., Fegan, C., Cartron, G., Knurowski, T., Saunders, A.J., Wright, J.G., Honda, H., Mazur, A., Yoshizawa, T., Kawabata, K. & Birkett, J.T. (2013) A phase I study of the oral Btk inhibitor ONO-4059 in patients with relapsed/refractory and high risk chronic lymphocytic leukaemia 11 (CLL). Blood (ASH Annual Meeting Abstracts), 122, 676.
57. Sanderson, K. (2013) Irreversible kinase inhibitors gain traction. Nature Reviews. Drug Discovery, 12, 649-651.
58. Smith, C.I., Baskin, B., Humire-Greiff, P., Zhou, J.N., Olsson, P.G., Maniar, H.S., Kjellen, P., Lambris, J.D., Christensson, B., Hammarstrom, L., Bentley, D., Vetrie, D., Islam, K.B., Vorechovsky, L. & Sideras, P. (1994) Expression of Bruton's agammaglobulinemia tyrosine kinase gene, BTK, is selectively down-regulated in T lymphocytes and plasma cells. Journal of Immunology, 152, 557-565.
59. Souers, A.J., Leverson, J.D., Boghaert, E.R., Ackler, S.L., Catron, N.D., Chen, J., Dayton, B.D., Ding, H., Enschede, S.H., Fairbrother, W.J., Huang, D.C., Hymowitz, S.G., Jin, S., Khaw, S.L., Kovar, P.J., Lam, L.T., Lee, J., Maecker, H.L., Marsh, K.C., Mason, K.D., Mitten, M.J., Nimmer, P.M., Oleksijew, A., Park, C.H., Park, C.M., Phillips, D.C., Roberts, A.W., Sampath, D., Seymour, J.F., Smith, M.L., Sullivan, G.M., Tahir, S.K., Tse, C., Wendt, M.D., Xiao, Y., Xue, J.C., Zhang, H., Humerickhouse, R.A., Rosenberg, S.H. & Elmore, S.W. (2013) ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nature Medicine, 19, 202-208.
60. Sporn, M.B. (1997) The war on cancer: a review. Annals of the New York Academy of Sciences, 833, 137-146.
61. Srinivasan, L., Sasaki, Y., Calado, D.P., Zhang, B., Paik, J.H., DePinho, R.A., Kutok, J.L., Kearney, J.F., Otipoby, K.L. & Rajewsky, K. (2009) PI3 kinase signals BCR-dependent mature B cell survival. Cell, 139, 573-586.
62. Stepensky, P., Weintraub, M., Yanir, A., Revel-Vilk, S., Krux, F., Huck, K., Linka, R.M., Shaag, A., Elpeleg, O., Borkhardt, A. & Resnick, I.B. (2011) IL-2-inducible T-cell kinase deficiency: clinical presentation and therapeutic approach. Haematologica, 96, 472-476.
63. Streubel, B., Vinatzer, U., Willheim, M., Raderer, M. & Chott, A. (2006) Novel t(5;9)(q33;q22) fuses ITK to SYK in unspecified peripheral T-cell lymphoma. Leukemia, 20, 313-318.
64. Tsukada, S., Saffran, D.C., Rawlings, D.J., Parolini, O., Allen, R.C., Klisak, I., Sparkes, R.S., Kubagawa, H., Mohandas, T., Quan, S., Belmont, J.W., Cooper, M.D., Conley, M.E. & Witte, O.N. (1993) Deficient expression of a B cell cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia. Cell, 72, 279-290.
65. Vaillant, F., Merino, D., Lee, L., Breslin, K., Pal, B., Ritchie, M.E., Smyth, G.K., Christie, M., Phillipson, L.J., Burns, C.J., Mann, G.B., Visvader, J.E. & Lindeman, G.J. (2013) Targeting BCL-2 with the BH3 mimetic ABT-199 in estrogen receptor-positive breast cancer. Cancer Cell, 24, 120-129.
66. Valiaho, J., Smith, C.I. & Vihinen, M. (2006) BTKbase: the mutation database for X-linked agammaglobulinemia. Human Mutation, 27, 1209-1217.
67. Vargas, L., Hamasy, A., Nore, B.F. & Smith, C.I. (2013) Inhibitors of BTK and ITK: state of the new drugs for cancer, autoimmunity and inflammatory diseases. Scandinavian Journal of Immunology, 78, 130-139.
68. Vetrie, D., Vorechovsky, I., Sideras, P., Holland, J., Davies, A., Flinter, F., Hammarstrom, L., Kinnon, C., Levinsky, R., Bobrow, M., Edvard-Smith, C.I. & Bentley, D.R. (1993) The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases. Nature, 361, 226-233.
69. deVos, S., Wilson, W., Gerecitano, J., Goy, A., Kenkre, V., Barr, P., Blum, K., Shustov, A., Advani, R., Fowler, N., Vose, J., Lih, C., Williams, M., Schmitz, R., Yang, Y., Pittaluga, S., Wright, G., Kunkel, L., McGreivy, J., Beaupre, D., Balasubramanian, S., Cheng, M., Moussa, D., Chang, L., Buggy, J. & Staudt, L. (2013) The Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib (PCI-32765), has preferential activity in the activated B cell-like (ABC) subtype of relapsed/refractory (R/R) DLBCL: interim phase 2 results. Haematologica, 98(s1), abstr S1180.
70. Vose, J.M., Habermann, T.M., Czuczman, M.S., Zinzani, P.L., Reeder, C.B., Tuscano, J.M., Lossos, I.S., Li, J., Pietronigro, D. & Witzig, T.E. (2013) Single-agent lenalidomide is active in patients with relapsed or refractory aggressive non-Hodgkin lymphoma who received prior stem cell transplantation. British Journal of Haematology, 162, 639-647.
71. de Weers, M., Verschuren, M.C., Kraakman, M.E., Mensink, R.G., Schuurman, R.K., van Dongen, J.J. & Hendriks, R.W. (1993) 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. European Journal of Immunology, 23, 3109-3114.
72. Yang, Y., Shaffer, A.L. 3rd, Emre, N.C., Ceribelli, M., Zhang, M., Wright, G., Xiao, W., Powell, J., Platig, J., Kohlhammer, H., Young, R.M., Zhao, H., Yang, Y., Xu, W., Buggy, J.J., Balasubramanian, S., Mathews, L.A., Shinn, P., Guha, R., Ferrer, M., Thomas, C., Waldmann, T.A. & Staudt, L.M. (2012) Exploiting synthetic lethality for the therapy of ABC diffuse large B cell lymphoma. Cancer Cell, 21, 723-737.
73. Yoshizawa, T., Birkett, J.T. & Kawabata, K. (2013) ONO-4059, a novel bruton's tyrosine kinase (Btk) inhibitor: synergistic activity in combination with chemotherapy in a ABC-DLBCL cell line. Blood, 122, 5151.
74. Young, R.M. & Staudt, L.M. (2013) Targeting pathological B cell receptor signalling in lymphoid malignancies. Nature Reviews. Drug Discovery, 12, 229-243.
75. Yu, L. & Smith, C.I. (2011) Tec family kinases. FEBS Journal, 278, 1969.