OSU-T315: A novel targeted therapeutic that antagonizes AKT membrane localization and activation of chronic lymphocytic leukemia cells

Blood

Volumn 125, Issue 2, 2015, Pages 284-295

  Liu, Ta Ming ^a   Ling, Yonghua ^b   Woyach, Jennifer A ^a   Beckwith, Kyle ^a   Yeh, Yuh Ying ^a   Hertlein, Erin ^a   Zhang, Xiaoli ^b   Lehman, Amy ^b   Awan, Farrukh ^a   Jones, Jeffrey A ^a   Andritsos, Leslie A ^a   Maddocks, Kami ^a   MacMurray, Jessica ^a   Salunke, Santosh B ^b   Chen, Ching Shih ^a,b   Phelps, Mitch A ^b   Byrd, John C ^a,b   Johnson, Amy J ^a,b  

^a THE OHIO STATE UNIVERSITY WEXNER MEDICAL CENTER   (United States)

^b OHIO STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA4 INTEGRIN; ANTINEOPLASTIC AGENT; B LYMPHOCYTE RECEPTOR; BRUTON TYROSINE KINASE INHIBITOR; CASPASE; CD40 ANTIGEN; OSU T315; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PROTEIN KINASE B; TOLL LIKE RECEPTOR 9; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; CELL DEATH; CELLULAR DISTRIBUTION; CHRONIC LYMPHATIC LEUKEMIA; CONTROLLED STUDY; CYTOLYSIS; CYTOTOXICITY; DRUG BIOAVAILABILITY; HUMAN; IMMUNOBLOTTING; IN VIVO STUDY; LEUKEMIA CELL; LIPID RAFT; MAXIMUM PLASMA CONCENTRATION; MEMBRANE BIOLOGY; MOUSE; MOUSE MODEL; NONHUMAN; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; SURVIVAL; TIME TO MAXIMUM PLASMA CONCENTRATION; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL SURVIVAL; DRUG EFFECTS; FLOW CYTOMETRY; METABOLISM; PROTEIN TRANSPORT; TRANSGENIC MOUSE;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL SURVIVAL; FLOW CYTOMETRY; HUMANS; IMMUNOBLOTTING; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; MICE; MICE, TRANSGENIC; PROTEIN TRANSPORT; PROTO-ONCOGENE PROTEINS C-AKT;

EID: 84920941596     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2014-06-583518     Document Type: Article

References (54)

1. Zenz T, Mertens D, Küppers R, Döhner H, Stilgenbauer S. From pathogenesis to treatment of chronic lymphocytic leukaemia. Nat Rev Cancer. 2010;10(1):37-50.
2. Chiorazzi N, Rai KR, Ferrarini M. Chronic lymphocytic leukemia. N Engl J Med. 2005;352(8):804-815.
3. Klein U, Dalla-Favera R. Germinal centres: role in B-cell physiology and malignancy. Nat Rev Immunol. 2008;8(1):22-33.
4. Zenz T, Mertens D, Döhner H, Stilgenbauer S. Importance of genetics in chronic lymphocytic leukemia. Blood Rev. 2011;25(3):131-137.
5. Hamblin TJ, Davis Z, Gardiner A, Oscier DG, Stevenson FK. Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood. 1999;94(6):1848-1854.
6. Damle RN, Wasil T, Fais F, et al. Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood. 1999;94(6):1840-1847.
7. Crespo M, Bosch F, Villamor N, et al. ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. N Engl J Med. 2003;348(18):1764-1775.
8. Hallek M, Fischer K, Fingerle-Rowson G, et al; International Group of Investigators; German Chronic Lymphocytic Leukaemia Study Group. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet. 2010;376(9747):1164-1174.
9. Robak T. GA-101, a third-generation, humanized and glyco-engineered anti-CD20 mAb for the treatment of B-cell lymphoid malignancies. Curr Opin Investig Drugs. 2009;10(6):588-596.
10. Döhner H, Stilgenbauer S, Benner A, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med. 2000;343(26):1910-1916.
11. Stephens DM, Ruppert AS, Jones JA, et al. Impact of targeted therapy on outcome of chronic lymphocytic leukemia patients with relapsed del(17p13.1) karyotype at a single center. Leukemia. 2014;28(6):1365-1368.
12. Burger JA, Ghia P, Rosenwald A, Caligaris-Cappio F. The microenvironment in mature B-cell malignancies: a target for new treatment strategies. Blood. 2009;114(16):3367-3375.
13. Herishanu Y, Pérez-Galán P, Liu D, et al. The lymph node microenvironment promotes B-cell receptor signaling, NF-kappaB activation, and tumor proliferation in chronic lymphocytic leukemia. Blood. 2011;117(2):563-574.
14. Dühren-von Minden M, Übelhart R, Schneider D, et al. Chronic lymphocytic leukaemia is driven by antigen-independent cell-autonomous signalling. Nature. 2012;489(7415):309-312.
15. Agathangelidis A, Darzentas N, Hadzidimitriou A, et al. Stereotyped B-cell receptors in one-third of chronic lymphocytic leukemia: a molecular classification with implications for targeted therapies. Blood. 2012;119(19):4467-4475.
16. Endo T, Nishio M, Enzler T, et al. BAFF and APRIL support chronic lymphocytic leukemia B-cell survival through activation of the canonical NF-kappaB pathway. Blood. 2007;109(2):703-710.
17. Rickert RC, Jellusova J, Miletic AV. Signaling by the tumor necrosis factor receptor superfamily in B-cell biology and disease. Immunol Rev. 2011;244(1):115-133.
18. Burger JA, Quiroga MP, Hartmann E, et al. Highlevel 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(13):3050-3058.
19. Möhle R, Failenschmid C, Bautz F, Kanz L. Overexpression of the chemokine receptor CXCR4 in B cell chronic lymphocytic leukemia is associated with increased functional response to stromal cell-derived factor-1 (SDF-1). Leukemia. 1999;13(12):1954-1959.
20. Dürig J, Schmücker U, Dührsen U. Differential expression of chemokine receptors in B cell malignancies. Leukemia. 2001;15(5):752-756.
21. Longo PG, Laurenti L, Gobessi S, Sica S, Leone G, Efremov DG. The Akt/Mcl-1 pathway plays a prominent role in mediating antiapoptotic signals downstream of the B-cell receptor in chronic lymphocytic leukemia B cells. Blood. 2008;111(2):846-855.
22. Hoellenriegel J, Meadows SA, Sivina M, et al. The phosphoinositide 39-kinase delta inhibitor, CAL-101, inhibits B-cell receptor signaling and chemokine networks in chronic lymphocytic leukemia. Blood. 2011;118(13):3603-3612.
23. Herman SE, Gordon AL, Hertlein E, et al. Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765. Blood. 2011;117(23):6287-6296.
24. Fresno Vara JA, Casado E, de Castro J, Cejas P, Belda-Iniesta C, González-Barón M. PI3K/Akt signalling pathway and cancer. Cancer Treat Rev. 2004;30(2):193-204.
25. Simons K, Toomre D. Lipid rafts and signal transduction. Nat Rev Mol Cell Biol. 2000;1(1):31-39.
26. Adam RM, Mukhopadhyay NK, Kim J, et al. Cholesterol sensitivity of endogenous and myristoylated Akt. Cancer Res. 2007;67(13):6238-6246.
27. Pham LV, Tamayo AT, Yoshimura LC, et al. A CD40 Signalosome anchored in lipid rafts leads to constitutive activation of NF-kappaB and autonomous cell growth in B cell lymphomas. Immunity. 2002;16(1):37-50.
28. Pierce SK. Lipid rafts and B-cell activation. Nat Rev Immunol. 2002;2(2):96-105.
29. Simons K, Ehehalt R. Cholesterol, lipid rafts, and disease. J Clin Invest. 2002;110(5):597-603.
30. Zhuang L, Kim J, Adam RM, Solomon KR, Freeman MR. Cholesterol targeting alters lipid raft composition and cell survival in prostate cancer cells and xenografts. J Clin Invest. 2005;115(4):959-968.
31. Zhuang L, Lin J, Lu ML, Solomon KR, Freeman MR. Cholesterol-rich lipid rafts mediate aktregulated survival in prostate cancer cells. Cancer Res. 2002;62(8):2227-2231.
32. Mollinedo F, de la Iglesia-Vicente J, Gajate C, et al. In vitro and In vivo selective antitumor activity of Edelfosine against mantle cell lymphoma and chronic lymphocytic leukemia involving lipid rafts. Clin Cancer Res. 2010;16(7):2046-2054.
33. McDonald PC, Fielding AB, Dedhar S. Integrinlinked kinase-essential roles in physiology and cancer biology. J Cell Sci. 2008;121(Pt 19):3121-3132.
34. Persad S, Attwell S, Gray V, et al. Regulation of protein kinase B/Akt-serine 473 phosphorylation by integrin-linked kinase: critical roles for kinase activity and amino acids arginine 211 and serine 343. J Biol Chem. 2001;276(29):27462-27469.
35. Huang Y, Li J, Zhang Y, Wu C. The roles of integrin-linked kinase in the regulation of myogenic differentiation. J Cell Biol. 2000;150(4):861-872.
36. Lee SL, Hsu EC, Chou CC, et al. Identification and characterization of a novel integrin-linked kinase inhibitor. J Med Chem. 2011;54(18):6364-6374.
37. Woyach JA, Bojnik E, Ruppert AS, et al. Bruton's tyrosine kinase (BTK) function is important to the development and expansion of chronic lymphocytic leukemia (CLL). Blood. 2014;123(8):1207-1213.
38. Smit LA, Hallaert DY, Spijker R, et al. Differential Noxa/Mcl-1 balance in peripheral versus lymph node chronic lymphocytic leukemia cells correlates with survival capacity. Blood. 2007;109(4):1660-1668.
39. Petlickovski A, Laurenti L, Li X, et al. Sustained signaling through the B-cell receptor induces Mcl-1 and promotes survival of chronic lymphocytic leukemia B cells. Blood. 2005;105(12):4820-4827.
40. Cross DA, Alessi DR, Cohen P, Andjelkovich M, Hemmings BA. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature. 1995;378(6559):785-789.
41. Casamayor A, Morrice NA, Alessi DR. Phosphorylation of Ser-241 is essential for the activity of 3-phosphoinositide-dependent protein kinase-1: identification of five sites of phosphorylation in vivo. Biochem J. 1999;342(Pt 2):287-292.
42. 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.
43. Burger JA, Tsukada N, Burger M, Zvaifler NJ, Dell'Aquila M, Kipps TJ. Blood-derived nurse-like cells protect chronic lymphocytic leukemia B cells from spontaneous apoptosis through stromal cellderived factor-1. Blood. 2000;96(8):2655-2663.
44. Kurtova AV, Balakrishnan K, Chen R, et al. Diverse marrow stromal cells protect CLL cells from spontaneous and drug-induced apoptosis: development of a reliable and reproducible system to assess stromal cell adhesion-mediated drug resistance. Blood. 2009;114(20):4441-4450.
45. Johnson AJ, Lucas DM, Muthusamy N, et al. Characterization of the TCL-1 transgenic mouse as a preclinical drug development tool for human chronic lymphocytic leukemia. Blood. 2006;108(4):1334-1338.
46. Pekarsky Y, Koval A, Hallas C, et al. Tcl1 enhances Akt kinase activity and mediates its nuclear translocation. Proc Natl Acad Sci USA. 2000;97(7):3028-3033.
47. Robak P, Robak T. A targeted therapy for protein and lipid kinases in chronic lymphocytic leukemia. Curr Med Chem. 2012;19(31):5294-5318.
48. Baracho GV, Miletic AV, Omori SA, Cato MH, Rickert RC. Emergence of the PI3-kinase pathway as a central modulator of normal and aberrant B cell differentiation. Curr Opin Immunol. 2011;23(2):178-183.
49. Herman SE, Gordon AL, Wagner AJ, et al. Phosphatidylinositol 3-kinase-d inhibitor CAL-101 shows promising preclinical activity in chronic lymphocytic leukemia by antagonizing intrinsic and extrinsic cellular survival signals. Blood. 2010;116(12):2078-2088.
50. IPI-145 shows promise in CLL patients. Cancer Discovery. 2014;4(2):136.
51. Mollinedo F, Fernández-Luna JL, Gajate C, et al. Selective induction of apoptosis in cancer cells by the ether lipid ET-18-OCH3 (Edelfosine): molecular structure requirements, cellular uptake, and protection by Bcl-2 and Bcl-X(L). Cancer Res. 1997;57(7):1320-1328.
52. Gajate C, Mollinedo F. Edelfosine and perifosine induce selective apoptosis in multiple myeloma by recruitment of death receptors and downstream signaling molecules into lipid rafts. Blood. 2007;109(2):711-719.
53. Larsson SC, Wolk A. Overweight and obesity and incidence of leukemia: a meta-analysis of cohort studies. Int J Cancer. 2008;122(6):1418-1421.
54. Woyach JA, Johnson AJ, Byrd JC. The B-cell receptor signaling pathway as a therapeutic target in CLL. Blood. 2012;120(6):1175-1184.