Bcl-xL-inhibitory BH3 mimetics can induce a transient thrombocytopathy that undermines the hemostatic function of platelets

Blood

Volumn 118, Issue 6, 2011, Pages 1663-1674

  Schoenwaelder, Simone M ^a   Jarman, Kate E ^a   Gardiner, Elizabeth E ^a   Hua, My ^a   Qiao, Jianlin ^a   White, Michael J ^b,c   Josefsson, Emma C ^c   Alwis, Imala ^a   Ono, Akiko ^a   Willcox, Abbey ^a   Andrews, Robert K ^a   Mason, Kylie D ^c   Salem, Hatem H ^a   Huang, David C S ^b,c   Kile, Benjamin T ^b,c   Roberts, Andrew W ^b,c   Jackson, Shaun P ^a  

^a MONASH UNIVERSITY   (Australia)

^b UNIVERSITY OF MELBOURNE   (Australia)

^c WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH   (Australia)

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; BH3 PROTEIN; GLYCOPROTEIN IB ALPHA; GLYCOPROTEIN VI; INTEGRIN; INTEGRIN ALPHA2B BETA3; NAVITOCLAX; PROTEIN BCL XL; UNCLASSIFIED DRUG; ABT-737; ADHESION RECEPTOR; ANILINE DERIVATIVE; BIPHENYL DERIVATIVE; COLLAGEN; FIBRINOGEN RECEPTOR; MEMBRANE PROTEIN; NITROPHENOL; PHOSPHATIDYLSERINE; PIPERAZINE DERIVATIVE; PLATELET MEMBRANE GLYCOPROTEIN VI; PROTEIN BCL X; SULFONAMIDE;

ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; BLEEDING TIME; CONTROLLED STUDY; DOSE RESPONSE; DOWN REGULATION; HEMOSTASIS; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; PRIORITY JOURNAL; THROMBOCYTE ADHESION; THROMBOCYTE AGGREGATION; THROMBOCYTOPATHY; ANIMAL; C57BL MOUSE; CHEMICALLY INDUCED DISORDER; DRUG ANTAGONISM; DRUG EFFECT; METABOLISM; PATHOPHYSIOLOGY; PHYSIOLOGY; SCANNING ELECTRON MICROSCOPY; THROMBOCYTE; THROMBOCYTE ADHESIVENESS; THROMBOCYTE COUNT; THROMBOCYTOPENIA; TIME; ULTRASTRUCTURE; WESTERN BLOTTING;

ANILINE COMPOUNDS; ANIMALS; APOPTOSIS; BCL-X PROTEIN; BIPHENYL COMPOUNDS; BLOOD PLATELETS; BLOTTING, WESTERN; COLLAGEN; DOSE-RESPONSE RELATIONSHIP, DRUG; DOWN-REGULATION; HEMOSTASIS; MEMBRANE GLYCOPROTEINS; MICE; MICE, INBRED C57BL; MICROSCOPY, ELECTRON, SCANNING; NITROPHENOLS; PHOSPHATIDYLSERINES; PIPERAZINES; PLATELET ADHESIVENESS; PLATELET AGGREGATION; PLATELET COUNT; PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX; PLATELET MEMBRANE GLYCOPROTEINS; SULFONAMIDES; THROMBOCYTOPENIA; TIME FACTORS;

EID: 80051606228     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2011-04-347849     Document Type: Article

References (46)

1. Lowe SW. Cancer therapy and p53. Curr Opin Oncol. 1995;7(6):547-553.
2. Reed JC. Regulation of apoptosis by bcl-2 family proteins and its role in cancer and chemoresistance. Curr Opin Oncol. 1995;7(6):541-546.
3. Levine AJ. The p53 tumor-suppressor gene. N Engl J Med. 1992;326(20):1350-1352.
4. Bader AG, Kang S, Zhao L, Vogt PK. Oncogenic PI3K deregulates transcription and translation. Nat Rev Cancer. 2005;5(12):921-929. (Pubitemid 41766781)
5. Karin M, Greten FR. NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol. 2005;5(10):749-759. (Pubitemid 41400849)
6. Reed JC, Pellecchia M. Apoptosis-based therapies for hematologic malignancies. Blood. 2005;106(2):408-418. (Pubitemid 40981231)
7. LaCasse EC, Mahoney DJ, Cheung HH, Plenchette S, Baird S, Korneluk RG. IAP-targeted therapies for cancer. Oncogene. 2008;27(48):6252-6275.
8. Chen F, Wang W, El-Deiry WS. Current strategies to target p53 in cancer. Biochem Pharmacol. 2010;80(5):724-730.
9. Engelman JA. Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer. 2009;9(8):550-562.
10. Zhang J, Yang PL, Gray NS. Targeting cancer with small molecule kinase inhibitors. Nat Rev Cancer. 2009;9(1):28-39.
11. Cragg MS, Harris C, Strasser A, Scott CL. Unleashing the power of inhibitors of oncogenic kinases through BH3 mimetics. Nat Rev Cancer. 2009;9(5):321-326.
12. Oltersdorf T, Elmore SW, Shoemaker AR, et al. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature. 2005;435(7042):677-681. (Pubitemid 40825512)
13. Shoemaker AR, Mitten MJ, Adickes J, et al. Activity of the Bcl-2 family inhibitor ABT-263 in a panel of small cell lung cancer xenograft models. Clin Cancer Res. 2008;14(11):3268-3277.
14. Shoemaker AR, Oleksijew A, Bauch J, et al. A small-molecule inhibitor of Bcl-XL potentiates the activity of cytotoxic drugs in vitro and in vivo. Cancer Res. 2006;66(17):8731-8739. (Pubitemid 44449190)
15. Mason KD, Vandenberg CJ, Scott CL, et al. In vivo efficacy of the Bcl-2 antagonist ABT-737 against aggressive Myc-driven lymphomas. Proc Natl Acad Sci U S A. 2008;105(46):17961-17966.
16. Bray K, Chen HY, Karp CM, et al. Bcl-2 modulation to activate apoptosis in prostate cancer. Mol Cancer Res. 2009;7(9):1487-1496.
17. High LM, Szymanska B, Wilczynska-Kalak U, et al. The Bcl-2 homology domain 3 mimetic ABT-737 targets the apoptotic machinery in acute lymphoblastic leukemia resulting in synergistic in vitro and in vivo interactions with established drugs. Mol Pharmacol. 2010;77(3):483-494.
18. Tagscherer KE, Fassl A, Campos B, et al. Apoptosis-based treatment of glioblastomas with ABT-737, a novel small molecule inhibitor of Bcl-2 family proteins. Oncogene. 2008;27(52):6646-6656.
19. Wilson WH, O'Connor OA, Czuczman MS, et al. Navitoclax, a targeted high-affinity inhibitor of BCL-2, in lymphoid malignancies: a phase 1 dose-escalation study of safety, pharmacokinetics, pharmacodynamics, and antitumour activity. Lancet Oncol. 2010;11(12):1149-1159.
20. Roberts AW, Seymour JF, Brown JR, et al. An ongoing phase 1/2a study of ABT-263; pharmacokinetics (PK), safety and anti-tumor activity in patients (pts) with relapsed or refractory chronic lymphocytic leukemia (CLL). Blood (ASH Annual Meeting Abstracts). 2009;114(22):Abstract 883.
21. Mason KD, Carpinelli MR, Fletcher JI, et al. Programmed anuclear cell death delimits platelet life span. Cell. 2007;128(6):1173-1186. (Pubitemid 46427871)
22. Tse C, Shoemaker AR, Adickes J, et al. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res. 2008;68(9):3421-3428.
23. Zhang H, Nimmer PM, Tahir SK, et al. Bcl-2 family proteins are essential for platelet survival. Cell Death Differ. 2007;14(5):943-951. (Pubitemid 46655455)
24. Bertino AM, Qi XQ, Li J, Xia Y, Kuter DJ. Apoptotic markers are increased in platelets stored at 37 degrees C. Transfusion. 2003;43(7):857-866. (Pubitemid 36753934)
25. Leytin V, Allen DJ, Mykhaylov S, Lyubimov E, Freedman J. Thrombin-triggered platelet apoptosis. J Thromb Haemost. 2006;4(12):2656-2663. (Pubitemid 44741562)
26. Schoenwaelder SM, Yuan Y, Josefsson EC, et al. Two distinct pathways regulate platelet phosphatidylserine exposure and procoagulant function. Blood. 2009;114(3):663-666.
27. Dale GL. Coated-platelets: an emerging component of the procoagulant response. J Thromb Haemost. 2005;3(10):2185-2192. (Pubitemid 41727196)
28. Kulkarni S, Jackson SP. Platelet factor XIII and calpain negatively regulate integrin alphaIIbbeta3 adhesive function and thrombus growth. J Biol Chem. 2004;279(29):30697-30706. (Pubitemid 38938002)
29. Roberts AW, Gandi L, O'Connor OO, et al. Reduction in platelet counts as mechanistic biomarker and guide for adaptive dose-escalation in Phase I studies of the Bcl-2 inhibitor ABT-263. J Clin Oncol. 2008;26:(May 20 suppl; abstract 3542).
30. Herbert JM, Bernat A, Maffrand JP. Aprotinin reduces clopidogrel-induced prolongation of the bleeding time in the rat. Thromb Res. 1993;71(6):433-441. (Pubitemid 23248664)
31. Jackson SP, Schoenwaelder SM, Goncalves I, et al. PI 3-kinase p110beta: a new target for antithrombotic therapy. Nat Med. 2005;11(5):507-514. (Pubitemid 40685973)
32. Denis C, Methia N, Frenette PS, et al. A mouse model of severe von Willebrand disease: defects in hemostasis and thrombosis. Proc Natl Acad Sci U S A. 1998;95(16):9524-9529. (Pubitemid 28506264)
33. Bauer M, Retzer M, Wilde JI, et al. Dichotomous regulation of myosin phosphorylation and shape change by Rho-kinase and calcium in intact human platelets. Blood. 1999;94(5):1665-1672. (Pubitemid 29411316)
34. Paul BZ, Daniel JL, Kunapuli SP. Platelet shape change is mediated by both calcium-dependent and -independent signaling pathways: role of p160 Rho-associated coiled-coil-containing protein kinase in platelet shape change. J Biol Chem. 1999;274(40):28293-28300.
35. Sebbagh M, Renvoize C, Hamelin J, Riche N, Bertoglio J, Breard J. Caspase-3-mediated cleavage of ROCK I induces MLC phosphorylation and apoptotic membrane blebbing. Nat Cell Biol. 2001;3(4):346-352. (Pubitemid 32288441)
36. Meredith JE Jr, Schwartz MA. Integrins, adhesion and apoptosis. Trends Cell Biol. 1997;7(4):146-150. (Pubitemid 27135573)
37. Gardiner EE, Karunakaran D, Shen Y, Arthur JF, Andrews RK, Berndt MC. Controlled shedding of platelet glycoprotein (GP)VI and GPIb-IX-V by ADAM family metalloproteinases. J Thromb Haemost. 2007;5(7):1530-1537. (Pubitemid 46965384)
38. Bergmeier W, Piffath CL, Cheng G, et al. Tumor necrosis factor-alpha-converting enzyme (ADAM17) mediates GPIbalpha shedding from platelets in vitro and in vivo. Circ Res. 2004;95(7):677-683. (Pubitemid 39331927)
39. Bodnar RJ, Gu M, Li Z, Englund GD, Du X. The cytoplasmic domain of the platelet glycoprotein Ibalpha is phosphorylated at serine 609. J Biol Chem. 1999;274(47):33474-33479. (Pubitemid 129511655)
40. Andrews RK, Karunakaran D, Gardiner EE, Berndt MC. Platelet receptor proteolysis: a mechanism for downregulating platelet reactivity. Arterioscler Thromb Vasc Biol. 2007;27(7):1511-1520. (Pubitemid 46986104)
41. Canault M, Duerschmied D, Brill A, et al. p38 mitogen- activated protein kinase activation during platelet storage: consequences for platelet recovery and hemostatic function in vivo. Blood. 2010;115(9):1835-1842.
42. Gardiner EE, Arthur JF, Kahn ML, Berndt MC, Andrews RK. Regulation of platelet membrane levels of glycoprotein VI by a platelet-derived metalloproteinase. Blood. 2004;104(12):3611-3617. (Pubitemid 39564435)
43. Chen H, Locke D, Liu Y, Liu C, Kahn ML. The platelet receptor GPVI mediates both adhesion and signaling responses to collagen in a receptor density-dependent fashion. J Biol Chem. 2002;277(4):3011-3019. (Pubitemid 34953338)
44. Jarvis GE, Best D, Watson SP. Differential roles of integrins alpha2beta1 and alphaIIbbeta3 in collagen and CRP-induced platelet activation. Platelets. 2004;15(5):303-313.
45. Fox JE. Cytoskeletal proteins and platelet signaling. Thromb Haemost. 2001;86(1):198-213. (Pubitemid 32666186)
46. Hayashi T, Mogami H, Murakami Y, et al. Real-time analysis of platelet aggregation and procoagulant activity during thrombus formation in vivo. Pflugers Arch. 2008;456(6):1239-1251.