Inhibition of IRAK1/4 sensitizes T cell acute lymphoblastic leukemia to chemotherapies

Journal of Clinical Investigation

Volumn 125, Issue 3, 2015, Pages 1081-1097

  Li, Zhaoyang ^a   Younger, Kenisha ^b   Gartenhaus, Ronald ^b,c   Joseph, Ann Mary ^b   Hu, Fang ^b   Baer, Maria R ^b,c   Brown, Patrick ^d   Davila, Eduardo ^b,c  

^a CHILDREN'S NATIONAL MEDICAL CENTER   (United States)

^b UNIVERSITY OF MARYLAND GREENEBAUM CANCER CENTER   (United States)

^c UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

^d JOHNS HOPKINS UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 [4 (4' CHLORO 2 BIPHENYLYLMETHYL) 1 PIPERAZINYL] N [4 [3 DIMETHYLAMINO 1 (PHENYLTHIOMETHYL)PROPYLAMINO] 3 NITROBENZENESULFONYL]BENZAMIDE; ANTINEOPLASTIC AGENT; INTERLEUKIN 1 RECEPTOR ASSOCIATED KINASE 1; INTERLEUKIN 1 RECEPTOR ASSOCIATED KINASE 1 INHIBITOR; INTERLEUKIN 1 RECEPTOR ASSOCIATED KINASE 4; INTERLEUKIN 1 RECEPTOR ASSOCIATED KINASE 4 INHIBITOR; INTERLEUKIN 8; MAMMALIAN TARGET OF RAPAMYCIN; MYELOID DIFFERENTIATION FACTOR 88; PATTERN RECOGNITION RECEPTOR; PHOSPHOPROTEIN; PROTEIN BCL XL; PROTEIN KINASE B; PROTEIN MCL 1; PROTEIN SERINE THREONINE KINASE INHIBITOR; SHORT HAIRPIN RNA; TOLL LIKE RECEPTOR 1; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR AGONIST; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 6; UBIQUITIN PROTEIN LIGASE E3; UNCLASSIFIED DRUG; VINCRISTINE; ABT-737; BENZIMIDAZOLE DERIVATIVE; BIPHENYL DERIVATIVE; INTERLEUKIN 1 RECEPTOR ASSOCIATED KINASE; IRAK1 PROTEIN, HUMAN; IRAK4 PROTEIN, HUMAN; MCL1 PROTEIN, HUMAN; NITROPHENOL; PIPERAZINE DERIVATIVE; SULFONAMIDE;

ACUTE LYMPHOBLASTIC LEUKEMIA; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CANCER COMBINATION CHEMOTHERAPY; CANCER GROWTH; CANCER RESISTANCE; CANCER SURVIVAL; CELL DEATH; CELL ISOLATION; CELL PROLIFERATION; CELL SURVIVAL; CHEMOSENSITIZATION; CLINICAL ARTICLE; COMPARATIVE STUDY; CONTROLLED STUDY; CYTOTOXICITY; DRUG EFFICACY; DRUG POTENTIATION; DRUG SCREENING; ENZYME INHIBITION; FEMALE; FOOD AND DRUG ADMINISTRATION; HUMAN; HUMAN CELL; MOUSE; MURINE LEUKEMIA; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN STABILITY; SIGNAL TRANSDUCTION; T CELL ACUTE LYMPHOBLASTIC LEUKEMIA; T CELL LEUKEMIA; T LYMPHOCYTE; UBIQUITINATION; ANIMAL; ANTAGONISTS AND INHIBITORS; C57BL MOUSE; DRUG EFFECTS; HEK293 CELL LINE; JURKAT CELL LINE; MCF 7 CELL LINE; METABOLISM; NONOBESE DIABETIC MOUSE; PRECURSOR T-CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; SCID MOUSE;

ANIMALS; ANTINEOPLASTIC AGENTS; BENZIMIDAZOLES; BIPHENYL COMPOUNDS; CELL PROLIFERATION; CELL SURVIVAL; DRUG SYNERGISM; FEMALE; HEK293 CELLS; HUMANS; INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASES; JURKAT CELLS; MCF-7 CELLS; MICE, INBRED C57BL; MICE, INBRED NOD; MICE, SCID; MYELOID CELL LEUKEMIA SEQUENCE 1 PROTEIN; NITROPHENOLS; PIPERAZINES; PRECURSOR T-CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; PROTEIN STABILITY; SULFONAMIDES; TNF RECEPTOR-ASSOCIATED FACTOR 6; VINCRISTINE; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84924086269     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI75821     Document Type: Article

References (64)

1. Dores GM, Devesa SS, Curtis RE, Linet MS, Morton LM. Acute leukemia incidence and patient survival among children and adults in the United States, 2001-2007. Blood. 2012;119(1):34-43.
2. Faderl S, et al. Adult acute lymphoblastic leukemia: concepts and strategies. Cancer. 2010;116(5):1165-1176.
3. Pui CH. T cell acute lymphoblastic leukemia: NOTCHing the way toward a better treatment outcome. Cancer Cell. 2009;15(2):85-87.
4. Bartholdy C, Christensen JE, Grujic M, Christensen JP, Thomsen AR. T-cell intrinsic expression of MyD88 is required for sustained expansion of the virus-specific CD8+ T-cell population in LCMV-infected mice. J Gen Virol. 2009;90(pt 2):423-431.
5. Geng D, et al. Amplifying TLR-MyD88 signals within tumor-specific T cells enhances antitumor activity to suboptimal levels of weakly immunogenic tumor antigens. Cancer Res. 2010;70(19):7442-7454.
6. Geng D, Zheng L, Srivastava R, Asprodites N, Velasco-Gonzalez C, Davila E. When Toll-like receptor and T-cell receptor signals collide: a mechanism for enhanced CD8 T-cell effector function. Blood. 2010;11 6(18):3494-3504.
7. LaRosa DF,et al T cell expression of MyD88 is required for resistance to Toxoplasma gondii Proc Natl Acad Sci U S A. 2008 105, 10, 3855-3860.
8. Quigley M, Martinez J, Huang X, Yang Y. A critical role for direct TLR2-MyD88 signaling in CD8 T-cell clonal expansion and memory formation following vaccinia viral infection. Blood. 2009;113(10):2256-2264.
9. Rahman AH, et al. MyD88 plays a critical T cellintrinsic role in supporting CD8 T cell expansion during acute lymphocytic choriomeningitis virus infection. J Immunol. 2008;181(6):3804-3810.
10. Zhao Y, De TC, Flynn R, Ware CF, Croft M, Salek-Ardakani S. The adaptor molecule MyD88 directly promotes CD8 T cell responses to vaccinia virus. J Immunol. 2009;182(10):6278-6286.
11. Akira S, Hemmi H. Recognition of pathogenassociated molecular patterns by TLR family. Immunol Lett. 2003;85(2):85-95.
12. Cheng H, et al. Regulation of IRAK-4 kinase activity via autophosphorylation within its activation loop. Biochem Biophys Res Commun. 2007;352(3):609-616.
13. Kollewe C, et al. Sequential autophosphorylation steps in the interleukin-1 receptor-Asso ciated kinase-1 regulate its availability as an adapter in interleukin-1 signaling. J Biol Chem. 2004;279(7):5227-5236.
14. Skaug B, Jiang X, Chen ZJ. The role of ubiquitin in NF-?B regulatory pathways. Annu Rev Biochem. 2009;78:769-796.
15. Linares JF, Duran A, Yajima T, Pasparakis M, Moscat J, Diaz-Meco MT. K63 polyubiquitination and activation of mTOR by the p62-TRAF6 complex in nutrient-Activated cells. Mol Cell. 2013;51(2):283-296.
16. Yang WL, et al. The E3 ligase TRAF6 regulates Akt ubiquitination and activation. Science. 2009;325(5944):1134-1138.
17. Mu Y, et al. TRAF6 ubiquitinates TGF? type I receptor to promote its cleavage and nuclear translocation in cancer. Nat Commun. 2011;2:330.
18. Suzuki N, et al. A critical role for the innate immune signaling molecule IRAK-4 in T cell activation. Science. 2006;311(5769):1927-1932.
19. McDonald DR, et al. Impaired T-cell receptor activation in IL-1 receptor-Associated kinase-4-deficient patients. J Allergy Clin Immunol. 2010;126(2):332-337.
20. Picard C, et al. Clinical features and outcome of patients with IRAK-4 and MyD88 deficiency. Medicine (Baltimore). 2010;89(6):403-425.
21. Asprodites N, Zheng L, Geng D, Velasco-Gonzalez C, Sanchez-Perez L, Davila E. Engagement of Toll-like receptor-2 on cytotoxic T-lymphocytes occurs in vivo and augments antitumor activity. FASEB J. 2008;22(10):3628-3637.
22. Bendigs S, Salzer U, Lipford GB, Wagner H, Heeg K. CpG-oligodeoxynucleotides co-stimulate primary T cells in the absence of antigen-presenting cells. Eur J Immunol. 1999;29(4):1209-1218.
23. Caron G, et al. Direct stim ulation of human T cells via TLR5 and TLR7/8: flagellin and R-848 up-regulate proliferation and IFN-gamma production by memory CD4+ T cells. J Immunol. 2005;175(3):1551-1557.
24. Cottalorda A, et al. TLR2 engagement on memory CD8(+) T cells improves their cytokine-mediated proliferation and IFN-? secretion in the absence of Ag. Eur J Immunol. 2009;39(10):2673-2681.
25. Komai-Koma M, Jones L, Ogg GS, Xu D, Liew FY. TLR2 is expressed on activated T cells as a costimulatory receptor. Proc Natl Acad Sci U S A. 2004;101(9):3029-3034.
26. Gelman AE, Zhang J, Choi Y, Turka LA. Toll-like receptor ligands directly promote activated CD4+ T cell survival. J Immunol. 2004;172(10):6065-6073.
27. Zheng L, Asprodites N, Keene AH, Rodriguez P, Brown KD, Davila E. TLR9 engagement on CD4 T lymphocytes represses {gamma}-radiation-induced apoptosis through activation of checkpoint kinase response elements. Blood. 2008;111(5):2704-2713.
28. Mollaki V, et al. Polymorphisms and haplotypes in TLR9 and MYD88 are associated with the development of Hodgkin's lymphoma: a candidate-gene association study. J Hum Genet. 2009;54(11):655-659.
29. Ngo VN, et al. Oncogenically active MYD88 mutations in human lymphoma. Nature. 2011;470(7332):115-119.
30. Yang G, et al. A mutation in MYD88 (L265P) supports the surviv al of lymphoplasmacytic cells by activation of Bruton tyrosine kinase in Waldenstrom macroglobulinemia. Blood. 2013;122(7):1222-1232.
31. Rhyasen GW, et al. Targeting IRAK1 as a Therapeutic Approach for Myelodysplastic Syndrome. Cancer Cell. 2013;24(1):90-104.
32. Barretina J, et al. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature. 2012;483(7391):603-607.
33. Cao Z, Henzel WJ, Gao X. IRAK: a kinase associated with the interleukin-1 receptor. Science. 1996;271(5252):1128-1131.
34. Li S, Strelow A, Fontana EJ, Wesche H. IRAK-4: a novel member of the IRAK family with the properties of an IRAK-kinase. Proc Natl Acad Sci U S A. 2002;99(8):5567-5572.
35. W ang Z, Wesche H, Stevens T, Walker N, Yeh WC. IRAK-4 inhibitors for inflammation. Curr Top Med Chem. 2009;9(8):724-737.
36. Fitzgerald KA, et al. Mal (MyD88-Adapter-like) is required for Toll-like receptor-4 signal transduction. Nature. 2001;413(6851):78-83.
37. Powers JP, et al. Discovery and initial SAR of inhibitors of interleukin-1 receptor-Associated kinase-4. Bioorg Med Chem Lett. 2006;16(11):2842-2845.
38. Chiaretti S, et al. Gene expression profile of adult T-cell acute lymphocytic leukemia identifies distinct subsets of patients with different response to th erapy and survival. Blood. 2004;103(7):2771-2778.
39. Derouet M, Thomas L, Cross A, Moots RJ, Edwards SW. Granulocyte macrophage colony-stimulating factor signaling and proteasome inhibi tion delay neutrophil apoptosis by increasing the stability of Mcl-1. J Biol Chem. 2004;279(26):26915-26921.
40. Henson ES, Gibson EM, Villanueva J, Bristow NA, Haney N, Gibson SB. I ncreased expression of Mcl-1 is responsible for the blockage of TRAILinduced apoptosis mediated by EGF/ErbB1 signaling pathway. J Cell Biochem. 2003;89(6):1177-1192.
41. Maurer U, Charvet C, Wagman A S, Dejardin E, Green DR. Glycogen synthase kinase-3 regulates mitochondrial outer membrane permeabilization and apoptosis by destabilization of MCL-1. Mol Cell. 2006;21(6):749-760.
42. Chao JR, et al. mcl-1 is an immediate-early gene activated by the granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling pathway and is one component of the GM-CSF viability response. Mol Cell Biol. 1998;18(8):4883-4 898.
43. Nijhawan D, et al. Elimination of Mcl-1 is required for the initiation of apoptosis following ultraviolet irradiation. Genes Dev. 2003;17(12):1475-1486.
44. Kohn AD, Takeuchi F, Roth RA. Akt, a pleckstrin homology domain containing kinase, is activated primarily by phosphorylation. J Biol Chem. 1996;271(36):21920-21926.
45. Mercurio F, et al. IKK-1 a nd IKK-2: cytokine-Activated IkappaB kinases essential for NF-kappaB activation. Science. 1997;278(5339):860-866.
46. Craig RW. MCL1 provides a window on the role of the BCL2 family in cell proliferation, differentiation and tumorigenesis. Leukemia. 2002;16(4):444-454.
47. Konopleva M, et al. MEK inhibition enhances ABT-737-induced leukemia cell apoptosis via prevention of ERK-Activated MCL-1 induction and modulation of MCL-1/BIM complex. Leukemia. 2012;26(4):778-787.
48. Weng AP, et al. Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science. 2004;306(5694):269-271.
49. Ferrando AA, et al. Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia. Cancer Cell. 2002;1(1):75-87.
50. Hebert J, Cayuela JM, Berkeley J, Sigaux F. Candidate tumor-suppressor gene s MTS1 (p16INK4A) and MTS2 (p15INK4B) display frequent homozygous deletions in primary cells from T-but not from B-cell lineage acute lymphoblastic leukemias. Blood. 1994;84(12):4038-4044.
51. Mizobe T, et al. Constitutive association of MyD88 to IRAK in HTLV-I-transformed T cells. Exp Hematol. 2007;35(12):1812-1822.
52. Matzinger P. Tolerance, danger, and the extended family. Annu Rev Immunol. 1994;12:991-1045.
53. Chen W, Syldath U, Bellmann K, Burkart V, Kolb H. Human 60-kDa heat-shock protein: a danger signal to the innate immune system. J Immunol. 1999;162(6):3212-3219.
54. Wallin RP, Lundqvist A, More SH, von BA, Kiessling R, Ljunggren HG. Heat-shock proteins as activators of the innate immune system. Trends Immunol. 2002;23(3):130-135 .
55. Vabulas RM, et al. Endocytosed HSP60s use toll-like receptor 2 (TLR2) and TLR4 to activate the toll/interleukin-1 receptor signaling pathway in innate immune cells. J Biol Chem. 2001;276(33):3 1332-31339.
56. Wheeler A, Archbold SM, Hardie T, Watson LM. Children with cochlear implants: the communication journey. Cochlear Implants Int. 2009;10(1):41-62.
57. v an der Heijden IM, et al. Presence of bacterial DNA and bacterial peptidoglycans in joints of patients with rheumatoid arthritis and other arthritides. Arthritis Rheum. 2000;43(3):593-598.
58. Sobek V, et al. Direct Toll-like receptor 2 mediated co-stimulation of T cells in the mouse system as a basis for chronic inflammatory joint disease. Arthritis Res Ther. 2004;6(5):R433-R446.
59. Smith TJ , et al. Differential expression of Toll-like receptors in follicular lymphoma, diffuse large B-cell lymphoma and peripheral T-cell lymphoma. Exp Mol Pathol. 2010;89(3):284-290.
60. Jarrousse V, Que reux G, Marques-Briand S, Knol AC, Khammari A, Dreno B. Toll-like receptors 2, 4 and 9 expression in cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome). Eur J Dermatol. 2006;16(6):636-641.
61. Liu H, et al. TRAF6 activation in multiple myeloma: a potential therapeutic target. Clin Lymphoma Myeloma Leuk. 2012;12(3):155-163.
62. Starczynowski DT, et al. TRAF6 is an amplified oncogene bridging the RAS and NF-kappaB pathways in human lung cancer. J Clin Invest. 2011;121(10):4095-4105.
63. Sun H, Li XB, Meng Y, Fan L, Li M, Fang J. TRAF6 upregulates expression of HIF-1alpha and promotes tumor angiogenesis. Cancer Res. 2013;73(15):4950-4959.
64. Yeoh EJ, et al. Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. Cancer Cell. 2002;1(2):133-143.