دورية أكاديمية
أعرض في EDS

Interleukin-1 receptor-associated kinase 4 inhibitor interrupts toll-like receptor signalling and sensitizes chronic lymphocytic leukaemia cells to apoptosis.

التفاصيل البيبلوغرافية
العنوان: Interleukin-1 receptor-associated kinase 4 inhibitor interrupts toll-like receptor signalling and sensitizes chronic lymphocytic leukaemia cells to apoptosis.
المؤلفون: Delvecchio VS; Cell signalling Unit, Division of Experimental Oncology, IRCCS San Raffaele Hospital, Milano, Italy., Sana I; Cell signalling Unit, Division of Experimental Oncology, IRCCS San Raffaele Hospital, Milano, Italy.; Università Vita-Salute San Raffaele, Milano, Italy., Mantione ME; Cell signalling Unit, Division of Experimental Oncology, IRCCS San Raffaele Hospital, Milano, Italy., Vilia MG; Cell signalling Unit, Division of Experimental Oncology, IRCCS San Raffaele Hospital, Milano, Italy., Ranghetti P; B-Cell Neoplasia Unit and Strategic Research Program on CLL, Division of Experimental Oncology, IRCCS San Raffaele Hospital, Milano, Italy., Rovida A; Università Vita-Salute San Raffaele, Milano, Italy.; B-Cell Neoplasia Unit and Strategic Research Program on CLL, Division of Experimental Oncology, IRCCS San Raffaele Hospital, Milano, Italy., Angelillo P; B-Cell Neoplasia Unit and Strategic Research Program on CLL, Division of Experimental Oncology, IRCCS San Raffaele Hospital, Milano, Italy., Scarfò L; Università Vita-Salute San Raffaele, Milano, Italy.; B-Cell Neoplasia Unit and Strategic Research Program on CLL, Division of Experimental Oncology, IRCCS San Raffaele Hospital, Milano, Italy., Ghia P; Università Vita-Salute San Raffaele, Milano, Italy.; B-Cell Neoplasia Unit and Strategic Research Program on CLL, Division of Experimental Oncology, IRCCS San Raffaele Hospital, Milano, Italy., Muzio M; Cell signalling Unit, Division of Experimental Oncology, IRCCS San Raffaele Hospital, Milano, Italy.
المصدر: British journal of haematology [Br J Haematol] 2020 May; Vol. 189 (3), pp. 475-488. Date of Electronic Publication: 2020 Feb 14.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 0372544 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2141 (Electronic) Linking ISSN: 00071048 NLM ISO Abbreviation: Br J Haematol Subsets: MEDLINE
أسماء مطبوعة: Publication: Oxford : Wiley-Blackwell
Original Publication: Oxford : Blackwell Scientific Publications
مواضيع طبية MeSH: Interleukin-1 Receptor-Associated Kinases/*therapeutic use , Leukemia, Lymphocytic, Chronic, B-Cell/*drug therapy , Toll-Like Receptors/*drug effects, Apoptosis ; Female ; Humans ; Interleukin-1 Receptor-Associated Kinases/pharmacology ; Male ; Signal Transduction
مستخلص: Chronic lymphocytic leukaemia (CLL) cells are strongly influenced by microenvironmental signals through the activation of distinct membrane receptors including the B-cell receptor and toll-like receptors (TLR). Recapitulating TLR stimulation in vitro by treating CLL cells with the TLR9 ligand CpG can induce metabolic activation and protection from apoptosis. We hypothesized that interfering with TLR signalling may be beneficial for treating CLL, and we tested in preclinical studies the effect of a specific interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitory small molecule on primary leukaemic cells isolated from the peripheral blood of patients. We observed that IRAK4, an upstream kinase of the TLR pathway, is expressed in patients with CLL, and lower IRAK4 mRNA levels associate with a better outcome. The specific IRAK4 inhibitor disrupted TLR signalling as assessed by reduction of the specific biomarkers NFKBIZ and interleukin-6 mRNAs, and restrained the protective effect of in vitro TLR stimulation on cell viability. To note, IRAK4 inhibitor induced p53 and triggered apoptosis. Co-treatment of CLL cells with increasing concentrations of IRAK4i and the Bruton tyrosine kinase inhibitor ibrutinib demonstrated a synergistic effect. Our results suggest that targetting IRAK4 may represent a novel approach in CLL and may be combined with other signalling inhibitors.
(© 2020 British Society for Haematology and John Wiley & Sons Ltd.)
References: Annemann, M., Plaza-Sirvent, C., Schuster, M., Katsoulis-Dimitriou, K., Kliche, S., Schraven, B. & Schmitz, I. (2016) Atypical IkappaB proteins in immune cell differentiation and function. Immunology Letters, 171, 26-35.
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, S3871-3878.
Bosshart, H. & Heinzelmann, M. (2016) THP-1 cells as a model for human monocytes. Annals of Translational Medicine, 4, 438.
Chiorazzi, N. & Efremov, D.G. (2013) Chronic lymphocytic leukemia: a tale of one or two signals? Cell Research, 23, 182-185.
Chou, T.C. (2010) Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Research, 70, 440-446.
Chou, T.C. & Talalay, P. (1984) Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Advances in Enzyme Regulation, 22, 27-55.
Chun, H.G., Leyland-Jones, B. & Cheson, B.D. (1991) Fludarabine phosphate: a synthetic purine antimetabolite with significant activity against lymphoid malignancies. Journal of Clinical Oncology, 9, 175-188.
Dadashian, E.L., McAuley, E.M., Liu, D., Shaffer, A.L. 3rd, Young, R.M., Iyer, J.R., Kruhlak, M.J., Staudt, L.M., Wiestner, A. & Herman, S.E.M. (2019) TLR signaling is activated in lymph node-resident CLL cells and is only partially inhibited by ibrutinib. Cancer Research, 79, 360-371.
De Nardo, D., Balka, K.R., Cardona Gloria, Y., Rao, V.R., Latz, E. & Masters, S.L. (2018) Interleukin-1 receptor-associated kinase 4 (IRAK4) plays a dual role in myddosome formation and Toll-like receptor signaling. Journal of Biological Chemistry, 293, 15195-15207.
Ding, W., Knox, T.R., Tschumper, R.C., Wu, W., Schwager, S.M., Boysen, J.C., Jelinek, D.F. & Kay, N.E. (2010) Platelet-derived growth factor (PDGF)-PDGF receptor interaction activates bone marrow-derived mesenchymal stromal cells derived from chronic lymphocytic leukemia: implications for an angiogenic switch. Blood, 116, 2984-2993.
Dunne, A., Carpenter, S., Brikos, C., Gray, P., Strelow, A., Wesche, H., Morrice, N. & O'Neill, L.A. (2010) IRAK1 and IRAK4 promote phosphorylation, ubiquitination, and degradation of MyD88 adaptor-like (Mal). Journal of Biological Chemistry, 285, 18276-18282.
Faul, F., Erdfelder, E., Lang, A.G. & Buchner, A. (2007) G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behavior Research Methods, 39, 175-191.
Flannery, S. & Bowie, A.G. (2010) The interleukin-1 receptor-associated kinases: critical regulators of innate immune signalling. Biochemical Pharmacology, 80, 1981-1991.
Fonte, E., Apollonio, B., Scarfo, L., Ranghetti, P., Fazi, C., Ghia, P., Caligaris-Cappio, F. & Muzio, M. (2013) In vitro sensitivity of CLL cells to fludarabine may be modulated by the stimulation of Toll-like receptors. Clinical Cancer Research, 19, 367-379.
Fonte, E., Vilia, M.G., Reverberi, D., Sana, I., Scarfo, L., Ranghetti, P., Orfanelli, U., Cenci, S., Cutrona, G., Ghia, P. & Muzio, M. (2017) Toll-like receptor 9 stimulation can induce IkappaBzeta expression and IgM secretion in chronic lymphocytic leukemia cells. Haematologica, 102, 1901-1912.
Fraczek, J., Kim, T.W., Xiao, H., Yao, J., Wen, Q., Li, Y., Casanova, J.L., Pryjma, J. & Li, X. (2008) The kinase activity of IL-1 receptor-associated kinase 4 is required for interleukin-1 receptor/toll-like receptor-induced TAK1-dependent NFkappaB activation. Journal of Biological Chemistry, 283, 31697-31705.
Ghia, P. & Cuneo, A. (2016) Ibrutinib in the real world patient: many lights and some shades. Haematologica, 101, 1448-1450.
Gimenez, N., Schulz, R., Higashi, M., Aymerich, M., Villamor, N., Delgado, J., Juan, M., Lopez-Guerra, M., Campo, E., Rosich, L., Seiffert, M. & Colomer, D. (2020) Targeting IRAK4 disrupts inflammatory pathways and delays tumor development in chronic lymphocytic leukemia. Leukemia, 34, 100-114.
Gutierrez, A. Jr, Tschumper, R.C., Wu, X., Shanafelt, T.D., Eckel-Passow, J., Huddleston, P.M. 3rd, Slager, S.L., Kay, N.E. & Jelinek, D.F. (2010) LEF-1 is a prosurvival factor in chronic lymphocytic leukemia and is expressed in the preleukemic state of monoclonal B-cell lymphocytosis. Blood, 116, 2975-2983.
Hallek, M., Cheson, B.D., Catovsky, D., Caligaris-Cappio, F., Dighiero, G., Dohner, H., Hillmen, P., Keating, M., Montserrat, E., Chiorazzi, N., Stilgenbauer, S., Rai, K.R., Byrd, J.C., Eichhorst, B., O'Brien, S., Robak, T., Seymour, J.F. & Kipps, T.J. (2018) Guidelines for diagnosis, indications for treatment, response assessment and supportive management of chronic lymphocytic leukemia. Blood, 131, 2754-2760.
Henault, M., Lee, L.N., Evans, G.F. & Zuckerman, S.H. (2005) The human Burkitt lymphoma cell line Namalwa represents a homogenous cell system characterized by high levels of Toll-like receptor 9 and activation by CpG oligonucleotides. Journal of Immunological Methods, 300, 93-99.
Herman, S.E., Gordon, A.L., Hertlein, E., Ramanunni, A., Zhang, X., Jaglowski, S., Flynn, J., Jones, J., Blum, K.A., Buggy, J.J., Hamdy, A., Johnson, A.J. & Byrd, J.C. (2011) Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765. Blood, 117, 6287-6296.
Herman, S.E., Mustafa, R.Z., Gyamfi, J.A., Pittaluga, S., Chang, S., Chang, B., Farooqui, M. & Wiestner, A. (2014) Ibrutinib inhibits BCR and NF-kappaB signaling and reduces tumor proliferation in tissue-resident cells of patients with CLL. Blood, 123, 3286-3295.
Herold, T., Jurinovic, V., Metzeler, K.H., Boulesteix, A.L., Bergmann, M., Seiler, T., Mulaw, M., Thoene, S., Dufour, A., Pasalic, Z., Schmidberger, M., Schmidt, M., Schneider, S., Kakadia, P.M., Feuring-Buske, M., Braess, J., Spiekermann, K., Mansmann, U., Hiddemann, W., Buske, C. & Bohlander, S.K. (2011) An eight-gene expression signature for the prediction of survival and time to treatment in chronic lymphocytic leukemia. Leukemia, 25, 1639-1645.
Kelly, P.N., Romero, D.L., Yang, Y., Shaffer, A.L. 3rd, Chaudhary, D., Robinson, S., Miao, W., Rui, L., Westlin, W.F., Kapeller, R. & Staudt, L.M. (2015) Selective interleukin-1 receptor-associated kinase 4 inhibitors for the treatment of autoimmune disorders and lymphoid malignancy. Journal of Experimental Medicine, 212, 2189-2201.
Kremlitzka, M., Macsik-Valent, B. & Erdei, A. (2016) Regulation of B cell functions by Toll-like receptors and complement. Immunology Letters, 178, 37-44.
Ku, C.L., von Bernuth, H., Picard, C., Zhang, S.Y., Chang, H.H., Yang, K., Chrabieh, M., Issekutz, A.C., Cunningham, C.K., Gallin, J., Holland, S.M., Roifman, C., Ehl, S., Smart, J., Tang, M., Barrat, F.J., Levy, O., McDonald, D., Day-Good, N.K., Miller, R., Takada, H., Hara, T., Al-Hajjar, S., Al-Ghonaium, A., Speert, D., Sanlaville, D., Li, X., Geissmann, F., Vivier, E., Marodi, L., Garty, B.Z., Chapel, H., Rodriguez-Gallego, C., Bossuyt, X., Abel, L., Puel, A. & Casanova, J.L. (2007) Selective predisposition to bacterial infections in IRAK-4-deficient children: IRAK-4-dependent TLRs are otherwise redundant in protective immunity. Journal of Experimental Medicine, 204, 2407-2422.
Kuppers, R. (2015) IRAK4 inhibition to shut down TLR signaling in autoimmunity and MyD88-dependent lymphomas. Journal of Experimental Medicine, 212, 2184.
Lee, J.H., Jeong, H., Choi, J.W., Oh, H. & Kim, Y.S. (2017) Clinicopathologic significance of MYD88 L265P mutation in diffuse large B-cell lymphoma: a meta-analysis. Scientific Reports, 7, 1785.
Longo, P.G., Laurenti, L., Gobessi, S., Petlickovski, A., Pelosi, M., Chiusolo, P., Sica, S., Leone, G. & Efremov, D.G. (2007) The Akt signaling pathway determines the different proliferative capacity of chronic lymphocytic leukemia B-cells from patients with progressive and stable disease. Leukemia, 21, 110-120.
Muzio, M., Scielzo, C., Bertilaccio, M.T., Frenquelli, M., Ghia, P. & Caligaris-Cappio, F. (2009) Expression and function of toll like receptors in chronic lymphocytic leukaemia cells. British Journal of Haematology, 144, 507-516.
Ntoufa, S., Vilia, M.G., Stamatopoulos, K., Ghia, P. & Muzio, M. (2016) Toll-like receptors signaling: a complex network for NF-κB activation in B-cell lymphoid malignancies. Seminars in Cancer Biology, 39, 15-25.
Picard, C., Puel, A., Bonnet, M., Ku, C.L., Bustamante, J., Yang, K., Soudais, C., Dupuis, S., Feinberg, J., Fieschi, C., Elbim, C., Hitchcock, R., Lammas, D., Davies, G., Al-Ghonaium, A., Al-Rayes, H., Al-Jumaah, S., Al-Hajjar, S., Al-Mohsen, I.Z., Frayha, H.H., Rucker, R., Hawn, T.R., Aderem, A., Tufenkeji, H., Haraguchi, S., Day, N.K., Good, R.A., Gougerot-Pocidalo, M.A., Ozinsky, A. & Casanova, J.L. (2003) Pyogenic bacterial infections in humans with IRAK-4 deficiency. Science, 299, 2076-2079.
de Rooij, M.F., Kuil, A., Geest, C.R., Eldering, E., Chang, B.Y., Buggy, J.J., Pals, S.T. & Spaargaren, M. (2012) The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia. Blood, 119, 2590-2594.
Stacchini, A., Aragno, M., Vallario, A., Alfarano, A., Circosta, P., Gottardi, D., Faldella, A., Rege-Cambrin, G., Thunberg, U., Nilsson, K. & Caligaris-Cappio, F. (1999) MEC1 and MEC2: two new cell lines derived from B-chronic lymphocytic leukaemia in prolymphocytoid transformation. Leukemia Research, 23, 127-136.
Suzuki, N., Suzuki, S., Duncan, G.S., Millar, D.G., Wada, T., Mirtsos, C., Takada, H., Wakeham, A., Itie, A., Li, S., Penninger, J.M., Wesche, H., Ohashi, P.S., Mak, T.W. & Yeh, W.C. (2002) Severe impairment of interleukin-1 and Toll-like receptor signalling in mice lacking IRAK-4. Nature, 416, 750-756.
Swantek, J.L., Tsen, M.F., Cobb, M.H. & Thomas, J.A. (2000) IL-1 receptor-associated kinase modulates host responsiveness to endotoxin. The Journal of Immunology, 164, 4301-4306.
Tarnani, M., Laurenti, L., Longo, P.G., Piccirillo, N., Gobessi, S., Mannocci, A., Marietti, S., Sica, S., Leone, G. & Efremov, D.G. (2010) The proliferative response to CpG-ODN stimulation predicts PFS, TTT and OS in patients with chronic lymphocytic leukemia. Leukemia Research, 34, 1189-1194.
Ten Hacken, E., Guieze, R. & Wu, C.J. (2017) SnapShot: chronic lymphocytic leukemia. Cancer Cell, 32, e711.
Thomas, J.A., Allen, J.L., Tsen, M., Dubnicoff, T., Danao, J., Liao, X.C., Cao, Z. & Wasserman, S.A. (1999) Impaired cytokine signaling in mice lacking the IL-1 receptor-associated kinase. The Journal of Immunology, 163, 978-984.
Tumey, L.N., Boschelli, D.H., Bhagirath, N., Shim, J., Murphy, E.A., Goodwin, D., Bennett, E.M., Wang, M., Lin, L.L., Press, B., Shen, M., Frisbie, R.K., Morgan, P., Mohan, S., Shin, J. & Rao, V.R. (2014) Identification and optimization of indolo[2,3-c]quinoline inhibitors of IRAK4. Bioorganic & Medicinal Chemistry Letters, 24, 2066-2072.
Wan, Y., Xiao, H., Affolter, J., Kim, T.W., Bulek, K., Chaudhuri, S., Carlson, D., Hamilton, T., Mazumder, B., Stark, G.R., Thomas, J. & Li, X. (2009) Interleukin-1 receptor-associated kinase 2 is critical for lipopolysaccharide-mediated post-transcriptional control. Journal of Biological Chemistry, 284, 10367-10375.
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.
معلومات مُعتمدة: 9965 International Associazione Italiana per la Ricerca sul Cancro; 16777 International Associazione Italiana per la Ricerca sul Cancro; 20246 International Associazione Italiana per la Ricerca sul Cancro; International Università Vita-Salute San Raffaele
فهرسة مساهمة: Keywords: Bruton's tyrosine kinase; chronic lymphocytic leukaemia; fludarabine; ibrutinib; interleukin-1 receptor-associated kinase 4; toll-like receptors
المشرفين على المادة: 0 (Toll-Like Receptors)
EC 2.7.11.1 (Interleukin-1 Receptor-Associated Kinases)
تواريخ الأحداث: Date Created: 20200215 Date Completed: 20210201 Latest Revision: 20210201
رمز التحديث: 20221213
DOI: 10.1111/bjh.16386
PMID: 32057093
قاعدة البيانات: MEDLINE
الوصف
تدمد:1365-2141
DOI:10.1111/bjh.16386