Mechanisms of ibrutinib resistance in chronic lymphocytic leukaemia and non-Hodgkin lymphoma

British Journal of Haematology

Volumn 170, Issue 4, 2015, Pages 445-456

  Zhang, Shuang Q ^a   Smith, Sonali M ^a   Zhang, Shuang Y ^b   Lynn Wang, Yue ^c  

^a UNIVERSITY OF CHICAGO   (United States)

^b EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF CHICAGO   (United States)

Author keywords

B cell receptor; Cell signalling; DNA mutation; Drug resistance; Lymphoid malignancy

Indexed keywords

BREAST CANCER RESISTANCE PROTEIN; BRUTON TYROSINE KINASE; CERDULATINIB; DASATINIB; IBRUTINIB; IDELALISIB; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; MYELOID DIFFERENTIATION FACTOR 88; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; AGAMMAGLOBULINAEMIA TYROSINE KINASE; PROTEIN KINASE INHIBITOR; PROTEIN TYROSINE KINASE; PYRAZOLE DERIVATIVE; PYRIMIDINE DERIVATIVE;

AMINO ACID SUBSTITUTION; BTK GENE; CANCER RESISTANCE; CHRONIC LYMPHATIC LEUKEMIA; DISEASE ACTIVITY; DRUG EFFICACY; ENZYME ACTIVITY; GENE; GENE MUTATION; HUMAN; LARGE CELL LYMPHOMA; MANTLE CELL LYMPHOMA; MYD88 GENE; NONHODGKIN LYMPHOMA; NONHUMAN; PATHOGENESIS; PLCG2 GENE; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION; TUMOR DIFFERENTIATION; WALDENSTROEM MACROGLOBULINEMIA; ANTAGONISTS AND INHIBITORS; DRUG RESISTANCE; ENZYMOLOGY; GENETICS; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; LYMPHOMA, NON-HODGKIN; METABOLISM; MUTATION; PATHOLOGY;

DRUG RESISTANCE, NEOPLASM; HUMANS; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; LYMPHOMA, NON-HODGKIN; MUTATION; PROTEIN KINASE INHIBITORS; PROTEIN-TYROSINE KINASES; PYRAZOLES; PYRIMIDINES;

EID: 84938546724     PISSN: 00071048     EISSN: 13652141     Source Type: Journal    
DOI: 10.1111/bjh.13427     Document Type: Review

References (65)

1. Advani, R.H., Buggy, J.J., Sharman, J.P., Smith, S.M., Boyd, T.E., Grant, B., Kolibaba, K.S., Furman, R.R., Rodriguez, S., Chang, B.Y., Sukbuntherng, J., Izumi, R., Hamdy, A., Hedrick, E. & Fowler, N.H. (2013) Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. Journal of Clinical Oncology, 31, 88-94.
2. Akinleye, A., Chen, Y., Mukhi, N., Song, Y. & Liu, D. (2013) Ibrutinib and novel BTK inhibitors in clinical development. Journal of Hematology & Oncology, 6, 59.
3. Alizadeh, A.A., Eisen, M.B., Davis, R.E., Ma, C., Lossos, I.S., Rosenwald, A., Boldrick, J.C., Sabet, H., Tran, T., Yu, X., Powell, J.I., Yang, L., Marti, G.E., Moore, T., Hudson, Jr, J., Lu, L., Lewis, D.B., Tibshirani, R., Sherlock, G., Chan, W.C., Greiner, T.C., Weisenburger, D.D., Armitage, J.O., Warnke, R., Levy, R., Wilson, W., Grever, M.R., Byrd, J.C., Botstein, D., Brown, P.O. & Staudt, L.M. (2000) Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature, 403, 503-511.
4. Amrein, P.C., Attar, E.C., Takvorian, T., Hochberg, E.P., Ballen, K.K., Leahy, K.M., Fisher, D.C., Lacasce, A.S., Jacobsen, E.D., Armand, P., Hasserjian, R.P., Werner, L., Neuberg, D. & Brown, J.R. (2011) Phase II study of dasatinib in relapsed or refractory chronic lymphocytic leukemia. Clinical Cancer Research, 17, 2977-2986.
5. Boyd, R.S., Jukes-Jones, R., Walewska, R., Brown, D., Dyer, M.J. & Cain, K. (2009) Protein profiling of plasma membranes defines aberrant signaling pathways in mantle cell lymphoma. Molecular & Cellular Proteomics: MCP, 8, 1501-1515.
6. Brown, J.R., Byrd, J.C., Coutre, S.E., Benson, D.M., Flinn, I.W., Wagner-Johnston, N.D., Spurgeon, S.E., Kahl, B.S., Bello, C., Webb, H.K., Johnson, D.M., Peterman, S., Li, D., Jahn, T.M., Lannutti, B.J., Ulrich, R.G., Yu, A.S., Miller, L.L. & Furman, R.R. (2014) Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110delta, for relapsed/refractory chronic lymphocytic leukemia. Blood, 123, 3390-3397.
7. Buggins, A.G. & Pepper, C.J. (2010) The role of Bcl-2 family proteins in chronic lymphocytic leukaemia. Leukemia Research, 34, 837-842.
8. Buggy, J.J. & Elias, L. (2012) Bruton tyrosine kinase (BTK) and its role in B-cell malignancy. International Reviews of Immunology, 31, 119-132.
9. Burger, J.A. & Chiorazzi, N. (2013) B cell receptor signaling in chronic lymphocytic leukemia. Trends in Immunology, 34, 592-601.
10. Burger, J.A., Keating, M.J., Wierda, W.G., Hartmann, E., Hoellenriegel, J., Rosin, N.Y., de Weerdt, I., Jeyakumar, G., Ferrajoli, A., Cardenas-Turanzas, M., Lerner, S., Jorgensen, J.L., Nogueras-Gonzalez, G.M., Zacharian, G., Huang, X., Kantarjian, H., Garg, N., Rosenwald, A. & O'Brien, S. (2014) Safety and activity of ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: a single-arm, phase 2 study. The Lancet. Oncology, 15, 1090-1099.
11. Byrd, J.C. (2014) Richter's transformation and CLL after ibrutinib: BTK and PLCg2 mutations. In: American Society of Hematology: Meeting on Lymphoma Biology (ed. by ASH), pp. 14. ASH, Colorado Springs, CO.
12. 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. (2013) Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. New England Journal of Medicine, 369, 32-42.
13. Cao, Y., Hunter, Z.R., Liu, X., Xu, L., Yang, G., Chen, J., Patterson, C.J., Tsakmaklis, N., Kanan, S., Rodig, S., Castillo, J.J. & Treon, S.P. (2015) The WHIM-like CXCR4(S338X) somatic mutation activates AKT and ERK, and promotes resistance to ibrutinib and other agents used in the treatment of Waldenstrom's macroglobulinemia. Leukemia, 29, 169-176.
14. Chang, B.Y., Furman, R.R., Zapatka, M., Barrientos, J.C., Li, D., Steggerda, S., Eckert, K., Francesco, M., Woyach, J.A., Johnson, A.J., James, D.F., Versele, M., Byrd, J.C., Stilgenbauer, S. & Buggy, J.J. (2013) Use of tumor genomic profiling to reveal mechanisms of resistance to the BTK inhibitor ibrutinib in chronic lymphocytic leukemia (CLL). Journal of Clinical Oncology (ASCO Meeting Abstracts), 31, 7014.
15. Chen, C.I., Gutierrez, M., de Nully Brown, P., Gabrail, N., Baz, R., Reece, D.E., Savona, M., Trudel, S., Siegel, D.S., Mau-Sorensen, M., Kuruvilla, J., Byrd, J.C., Shacham, S., Rashal, T., Yau, C.Y., McCauley, D., Saint-Martin, J.R., McCartney, J., Landesman, Y., Klebanov, B., Pond, G., Oza, A.M., Kauffman, M. & Mirza, M.R. (2013) Anti tumor activity of selinexor (KPT-330), a first-in-class oral selective inhibitor of nuclear export (SINE) XPO1/CRM1 antagonist in patients (pts) with relapsed/refractory multiple myeloma (MM) or Waldenstrom's macroglobulinemia (WM). Blood, 122, 1942.
16. Cheng, S., Ma, J., Guo, A., Lu, P., Leonard, J.P., Coleman, M., Liu, M., Buggy, J.J., Furman, R.R. & Wang, Y.L. (2014a) BTK inhibition targets in vivo CLL proliferation through its effects on B-cell receptor signaling activity. Leukemia, 28, 649-657.
17. Cheng, S., Guo, A., Lu, P., Ma, J., Coleman, M. & Wang, Y.L. (2014b) Functional characterization of BTK mutation that confers ibrutinib resistance: exploration of alternative kinase inhibitors. Leukemia, 28, 649-657.
18. Chiron, D., Di Liberto, M., Martin, P., Huang, X., Sharman, J., Blecua, P., Mathew, S., Vijay, P., Eng, K., Ali, S., Johnson, A., Chang, B., Ely, S., Elemento, O., Mason, C.E., Leonard, J.P. & Chen-Kiang, S. (2014) Cell-cycle reprogramming for PI3K inhibition overrides a relapse-specific C481S BTK mutation revealed by longitudinal functional genomics in mantle cell lymphoma. Cancer Discovery, 4, 1022-1035.
19. Chitta, K., Paulus, A., Caulfield, T.R., Akhtar, S., Blake, M.K., Ailawadhi, S., Knight, J., Heckman, M.G., Pinkerton, A. & Chanan-Khan, A. (2014) Nimbolide targets BCL2 and induces apoptosis in preclinical models of Waldenstroms macroglobulinemia. Blood Cancer Journal, 4, e260.
20. Cinar, M., Hamedani, F., Mo, Z., Cinar, B., Amin, H.M. & Alkan, S. (2013) Bruton tyrosine kinase is commonly overexpressed in mantle cell lymphoma and its attenuation by ibrutinib induces apoptosis. Leukemia Research, 37, 1271-1277.
21. Dal Porto, J.M., Gauld, S.B., Merrell, K.T., Mills, D., Pugh-Bernard, A.E. & Cambier, J. (2004) B cell antigen receptor signaling 101. Molecular Immunology, 41, 599-613.
22. Davids, M.S. & Letai, A. (2013) ABT-199: taking dead aim at BCL-2. Cancer Cell, 23, 139-141.
23. Davids, M.S., Roberts, A.W., Anderson, M., Pagel, J.M., Kahl, B.S., Gerecitano, J.F., Darden, D.E., Nolan, C.E., Gressick, L.A., Yang, J., Chyla, B.J., Busman, T.A., Graham, A.M., Cerri, E., Enschede, S.H., Humerickhouse, R.A. & Seymour, J.F. (2012) The BCL-2-specific BH3-mimetic ABT-199 (GDC-0199) is active and well-tolerated in patients with relapsed non-Hodgkin lymphoma: interim results of a phase I study. Blood, 120, 304.
24. 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.
25. 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.
26. Flinn, I., Patel, M.R., Wagner-Johnston, N.D., Pandey, A., Coffey, G., Leeds, J., Hollenbach, S., Russell, S., Baker, D., Levy, G.G. & Curnutte, J.T. (2014) Pharmacokinetics and pharmacodynamics of the dual syk/jak inhibitor PRT062070 (cerdulatinib) in patients with advanced B-cell malignancies. Journal of Clinical Oncology, 32, 2619.
27. Foa, R. (2014) Changes in the treatment landscape for chronic lymphoid leukemia. New England Journal of Medicine, 371, 273-274.
28. Friedberg, J.W., Sharman, J., Sweetenham, J., Johnston, P.B., Vose, J.M., Lacasce, A., Schaefer-Cutillo, J., De Vos, S., Sinha, R., Leonard, J.P., Cripe, L.D., Gregory, S.A., Sterba, M.P., Lowe, A.M., Levy, R. & Shipp, M.A. (2010) Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia. Blood, 115, 2578-2585.
29. Furman, R.R., Cheng, S., Lu, P., Setty, M., Perez, A.R., Guo, A., Racchumi, J., Xu, G., Wu, H., Ma, J., Steggerda, S.M., Coleman, M., Leslie, C. & Wang, Y.L. (2014a) Ibrutinib resistance in chronic lymphocytic leukemia. New England Journal of Medicine, 370, 2352-2354.
30. Furman, R.R., Sharman, J.P., Coutre, S.E., Cheson, B.D., Pagel, J.M., Hillmen, P., Barrientos, J.C., Zelenetz, A.D., Kipps, T.J., Flinn, I., Ghia, P., Eradat, H., Ervin, T., Lamanna, N., Coiffier, B., Pettitt, A.R., Ma, S., Stilgenbauer, S., Cramer, P., Aiello, M., Johnson, D.M., Miller, L.L., Li, D., Jahn, T.M., Dansey, R.D., Hallek, M. & O'Brien, S.M. (2014b) Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. New England Journal of Medicine, 370, 997-1007.
31. Gerecitano, J. (2014) SINE (selective inhibitor of nuclear export) inverted question mark translational science in a new class of anti-cancer agents. Journal of Hematology & Oncology, 7, 67.
32. Guarini, A., Chiaretti, S., Tavolaro, S., Maggio, R., Peragine, N., Citarella, F., Ricciardi, M.R., Santangelo, S., Marinelli, M., De Propris, M.S., Messina, M., Mauro, F.R., Del Giudice, I. & Foa, R. (2008) BCR ligation induced by IgM stimulation results in gene expression and functional changes only in IgV H unmutated chronic lymphocytic leukemia (CLL) cells. Blood, 112, 782-792.
33. Herman, S.E., Barr, P.M., McAuley, E.M., Liu, D., Wiestner, A. & Friedberg, J.W. (2013) Fostamatinib inhibits B-cell receptor signaling, cellular activation and tumor proliferation in patients with relapsed and refractory chronic lymphocytic leukemia. Leukemia, 27, 1769-1773.
34. 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.
35. Hunter, Z.R., Xu, L., Yang, G., Zhou, Y., Liu, X., Cao, Y., Manning, R.J., Tripsas, C., Patterson, C.J., Sheehy, P. & Treon, S.P. (2014) The genomic landscape of Waldenstrom macroglobulinemia is characterized by highly recurring MYD88 and WHIM-like CXCR4 mutations, and small somatic deletions associated with B-cell lymphomagenesis. Blood, 123, 1637-1646.
36. Intlekofer, A.M. & Younes, A. (2014) Precision therapy for lymphoma - current state and future directions. Nature Reviews. Clinical Oncology, 11, 585-596.
37. Jhaveri, K., Taldone, T., Modi, S. & Chiosis, G. (2012) Advances in the clinical development of heat shock protein 90 (Hsp90) inhibitors in cancers. Biochimica et Biophysica Acta, 1823, 742-755.
38. Kurosaki, T., Shinohara, H. & Baba, Y. (2010) B cell signaling and fate decision. Annual Review of Immunology, 28, 21-55.
39. Kuruvilla, J., Gutierrez, M., Shah, B.D., Gabrail, N.Y., de Nully Brown, P., Stone, R.M., Garzon, R., Savona, M., Siegel, D.S., Baz, R., Mau-Sorensen, M., Davids, M.S., Byrd, J.C., Shacham, S., Rashal, T., Yau, C.Y.F., McCauley, D., Saint-Martin, J.-R., McCartney, J., Landesman, Y., Klebanov, B., Pond, G., Oza, A.M., Kauffman, M. & Mirza, M.R. (2013) Preliminary evidence of anti tumor activity of selinexor (KPT-330) in a phase I trial Ofa first-in-class oral Selective Inhibitor of Nuclear Export (SINE) in patients (pts) with relapsed/refractory Non Hodgkin's lymphoma (NHL) and chronic lymphocytic L. Blood, 122, 90.
40. Kuruvilla, J., Byrd, J.C., Flynn, J.M., Garzon, R., Porcu, P., Wagner-Johnston, N., Savoie, M.L., Stone, R.M., Jacobsen, E.D., Mau-Sorensen, M., de Nully Brown, P., Baz, R., Shal, B., Flinn, I., Gabrail, N., Kukreti, V., Tiedemann, R.E., Landesman, Y., Klebanov, B., Shacham, E., Saint-Martin, J.R., Marshall, T., McCartney, J., McCauley, D., Carlson, R., Norori, S., Savona, M.R., Rashal, T., Mirza, M.R., Kauffman, M. & Shacham, S. (2014) The oral Selective Inhibitor of Nuclear Export (SINE) selinexor (KPT-330) demonstrates broad and durable clinical activity in relapsed/refractory Non Hodgkin's Lymphoma (NHL). Blood, 124, 396.
41. Ma, J., Lu, P., Guo, A., Cheng, S., Zong, H., Martin, P., Coleman, M. & Wang, Y.L. (2014) Characterization of ibrutinib-sensitive and -resistant mantle lymphoma cells. British Journal of Haematology, 166, 849-861.
42. Macias-Perez, I.M. & Flinn, I.W. (2012) B-cell receptor pathobiology and targeting in NHL. Current Oncology Reports, 14, 411-418.
43. Mahajan, S., Ghosh, S., Sudbeck, E.A., Zheng, Y., Downs, S., Hupke, M. & Uckun, F.M. (1999) 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]. Journal of Biological Chemistry, 274, 9587-9599.
44. Mohamed, A.J., Yu, L., Backesjo, C.M., Vargas, L., Faryal, R., Aints, A., Christensson, B., Berglof, A., Vihinen, M., Nore, B.F. & Smith, C.I. (2009) Bruton's tyrosine kinase (Btk): function, regulation, and transformation with special emphasis on the PH domain. Immunological Reviews, 228, 58-73.
45. Novero, A., Ravella, P.M., Chen, Y., Dous, G. & Liu, D. (2014) Ibrutinib for B cell malignancies. Experimental Hematology & Oncology, 3, 4.
46. 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.
47. Ponader, S., Chen, S.S., Buggy, J.J., Balakrishnan, K., Gandhi, V., Wierda, W.G., Keating, M.J., O'Brien, S., Chiorazzi, N. & Burger, J.A. (2012) The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo. Blood, 119, 1182-1189.
48. Rahal, R., Frick, M., Romero, R., Korn, J.M., Kridel, R., Chan, F.C., Meissner, B., Bhang, H.E., Ruddy, D., Kauffmann, A., Farsidjani, A., Derti, A., Rakiec, D., Naylor, T., Pfister, E., Kovats, S., Kim, S., Dietze, K., Dorken, B., Steidl, C., Tzankov, A., Hummel, M., Monahan, J., Morrissey, M.P., Fritsch, C., Sellers, W.R., Cooke, V.G., Gascoyne, R.D., Lenz, G. & Stegmeier, F. (2014) Pharmacological and genomic profiling identifies NF-kappaB-targeted treatment strategies for mantle cell lymphoma. Nature Medicine, 20, 87-92.
49. Rinaldi, A., Kwee, I., Taborelli, M., Largo, C., Uccella, S., Martin, V., Poretti, G., Gaidano, G., Calabrese, G., Martinelli, G., Baldini, L., Pruneri, G., Capella, C., Zucca, E., Cotter, F.E., Cigudosa, J.C., Catapano, C.V., Tibiletti, M.G. & Bertoni, F. (2006) Genomic and expression profiling identifies the B-cell associated tyrosine kinase Syk as a possible therapeutic target in mantle cell lymphoma. British Journal of Haematology, 132, 303-316.
50. Rosenwald, A., Wright, G., Chan, W.C., Connors, J.M., Campo, E., Fisher, R.I., Gascoyne, R.D., Muller-Hermelink, H.K., Smeland, E.B., Giltnane, J.M., Hurt, E.M., Zhao, H., Averett, L., Yang, L., Wilson, W.H., Jaffe, E.S., Simon, R., Klausner, R.D., Powell, J., Duffey, P.L., Longo, D.L., Greiner, T.C., Weisenburger, D.D., Sanger, W.G., Dave, B.J., Lynch, J.C., Vose, J., Armitage, J.O., Montserrat, E., Lopez-Guillermo, A., Grogan, T.M., Miller, T.P., LeBlanc, M., Ott, G., Kvaloy, S., Delabie, J., Holte, H., Krajci, P., Stokke, T. & Staudt, L.M.; Lymphoma/Leukemia Molecular Profiling Project. (2002) The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. New England Journal of Medicine, 346, 1937-1947.
51. Rosenwald, A., Wright, G., Leroy, K., Yu, X., Gaulard, P., Gascoyne, R.D., Chan, W.C., Zhao, T., Haioun, C., Greiner, T.C., Weisenburger, D.D., Lynch, J.C., Vose, J., Armitage, J.O., Smeland, E.B., Kvaloy, S., Holte, H., Delabie, J., Campo, E., Montserrat, E., Lopez-Guillermo, A., Ott, G., Muller-Hermelink, H.K., Connors, J.M., Braziel, R., Grogan, T.M., Fisher, R.I., Miller, T.P., LeBlanc, M., Chiorazzi, M., Zhao, H., Yang, L., Powell, J., Wilson, W.H., Jaffe, E.S., Simon, R., Klausner, R.D. & Staudt, L.M. (2003) Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. Journal of Experimental Medicine, 198, 851-862.
52. Savona, M., Garzon, R., de Nully Brown, P., Yee, K., Lancet, J.E., Gutierrez, M., Gabrail, N., Mau-Sorensen, M., Baz, R., Byrd, J.C., Kuruvilla, J., Siegel, D.S., Shacham, S., Rashal, T., Yau, C.Y., McCauley, D., Saint-Martin, J.R., McCartney, J., Landesman, Y., Klebanov, B., Pond, G., Oza, A.M., Kauffman, M., Mirza, M.R. & Stone, R.M. (2013) Phase I trial of selinexor (KPT-330), a first-in-class oral Selective Inhibitor of Nuclear Export (SINE) in patients (pts) with advanced Acute Myelogenous Leukemia (AML). Blood, 122, 1440.
53. Staudt, L.M. (2010) Oncogenic activation of NF-kappaB. Cold Spring Harbor Perspectives in Biology, 2, a000109.
54. Staudt, L.M. (2014) Targeting pathological B-cell receptor signaling therapeutically. In: American Society of Hematology: Meeting on Lymphoma Biology. (ed. by ASH), pp. 14-15. ASH, Colorado Springs, CO.
55. Treon, S.P. & Hunter, Z.R. (2013) A new era for Waldenstrom macroglobulinemia: MYD88 L265P. Blood, 121, 4434-4436.
56. Treon, S.P., Xu, L., Yang, G., Zhou, Y., Liu, X., Cao, Y., Sheehy, P., Manning, R.J., Patterson, C.J., Tripsas, C., Arcaini, L., Pinkus, G.S., Rodig, S.J., Sohani, A.R., Harris, N.L., Laramie, J.M., Skifter, D.A., Lincoln, S.E. & Hunter, Z.R. (2012) MYD88 L265P somatic mutation in Waldenstrom's macroglobulinemia. New England Journal of Medicine, 367, 826-833.
57. Treon, S.P., Tripasas, C.K., Yang, G., Cao, Y., Xu, L., Hunter, Z., Cropper, S.J., Mostyn, P., Meid, K., Warren, D., Patterson, C., Varma, G., Laubach, J.P., Paba-Prada, C.E., Kunsman, J., Ghobrial, I.M., Kanan, S., Advani, R.H. & Palomba, M.L. (2013) A prospective multicenter study of the Bruton's tyrosine kinase inhibitor ibrutinib in patients with relapsed or refractory Waldenstrom's macroglobulinemia. Blood, 122, 251.
58. Trepel, J., Mollapour, M., Giaccone, G. & Neckers, L. (2010) Targeting the dynamic HSP90 complex in cancer. Nature Reviews Cancer, 10, 537-549.
59. Wang, M.L., Rule, S., Martin, P., Goy, A., Auer, R., Kahl, B.S., Jurczak, W., Advani, R.H., Romaguera, J.E., Williams, M.E., Barrientos, J.C., Chmielowska, E., Radford, J., Stilgenbauer, S., Dreyling, M., Jedrzejczak, W.W., Johnson, P., Spurgeon, S.E., Li, L., Zhang, L., Newberry, K., Ou, Z., Cheng, N., Fang, B., McGreivy, J., Clow, F., Buggy, J.J., Chang, B.Y., Beaupre, D.M., Kunkel, L.A. & Blum, K.A. (2013) Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. New England Journal of Medicine, 369, 507-516.
60. Wilson, W., Gerecitano, J., Goy, A., de Vos, S., Kenkre, V., Barr, P., Blum, K., Shustov, A., Advani, R., Lih, J., Williams, M., Schmitz, R., Yang, Y., Pittaluga, S., Wright, G., Kunkel, L., McGreivy, J., Balasubramanian, S., Cheng, M., Moussa, J., Buggy, J. & Staudt, L. (2012) The Bruton's Tyrosine Kinase (BTK) inhibitor, ibrutinib (PCI-32765), has preferential activity in the ABC subtype of relapsed/refractory de novo diffuse large B-cell lymphoma (DLBCL): interim results of a multicenter, open-label, phase 2 study. Blood, 120, 686.
61. Woyach, J.A., Furman, R.R., Liu, T.M., Ozer, H.G., Zapatka, M., Ruppert, A.S., Xue, L., Li, D.H., Steggerda, S.M., Versele, M., Dave, S.S., Zhang, J., Yilmaz, A.S., Jaglowski, S.M., Blum, K.A., Lozanski, A., Lozanski, G., James, D.F., Barrientos, J.C., Lichter, P., Stilgenbauer, S., Buggy, J.J., Chang, B.Y., Johnson, A.J. & Byrd, J.C. (2014) Resistance mechanisms for the Bruton's tyrosine kinase inhibitor ibrutinib. New England Journal of Medicine, 370, 2286-2294.
62. Wright, G., Tan, B., Rosenwald, A., Hurt, E.H., Wiestner, A. & Staudt, L.M. (2003) A gene expression-based method to diagnose clinically distinct subgroups of diffuse large B cell lymphoma. Proceedings of the National Academy of Sciences of the United States of America, 100, 9991-9996.
63. Yang, G., Zhou, Y., Liu, X., Xu, L., Cao, Y., Manning, R.J., Patterson, C.J., Buhrlage, S.J., Gray, N., Tai, Y.T., Anderson, K.C., Hunter, Z.R. & Treon, S.P. (2013) A mutation in MYD88 (L265P) supports the survival of lymphoplasmacytic cells by activation of Bruton tyrosine kinase in Waldenstrom macroglobulinemia. Blood, 122, 1222-1232.
64. Young, R.M. & Staudt, L.M. (2013) Targeting pathological B cell receptor signalling in lymphoid malignancies. Nature Reviews. Drug Discovery, 12, 229-243.
65. Zhou, Q., Lee, G.S., Brady, J., Datta, S., Katan, M., Sheikh, A., Martins, M.S., Bunney, T.D., Santich, B.H., Moir, S., Kuhns, D.B., Long Priel, D.A., Ombrello, A., Stone, D., Ombrello, M.J., Khan, J., Milner, J.D., Kastner, D.L. & Aksentijevich, I. (2012) A hypermorphic missense mutation in PLCG2, encoding phospholipase Cgamma2, causes a dominantly inherited autoinflammatory disease with immunodeficiency. American Journal of Human Genetics, 91, 713-720.