Best Practice & Research Clinical Haematology
Volume 21, Issue 1 , Pages 5-11 , March 2008

Apoptosis in leukemia: From molecular pathways to targeted therapies

  • Aaron D. Schimmer, MD, PhD, FRCPC (Staff Physician and Scientist)

      Affiliations

    • Corresponding Author InformationTel: (416) 946 2838; Fax: (416) 946 6546.

References 

  1. Schimmer AD, Hedley DW, Penn LZ, et al. Receptor- and mitochondrial-mediated apoptosis in acute leukemia: a translational view. Blood. 2001;98:3541–3553
  2. Schimmer AD. Inhibitor of apoptosis proteins: translating basic knowledge into clinical practice. Cancer Research. 2004;64:7183–7190
  3. Schimmer AD, Munk-Pedersen I, Minden MD, et al. BCL2 and apoptosis in chronic lymphocytic leukemia. Current Treatment Options in Oncology. 2003;4:211–218
  4. Schimmer AD, Dalili S, Batey RA, et al. Targeting XIAP for the treatment of malignancy. Cell Death Differ. 2006;13:179–188
  5. Reed JC. Proapoptotic multidomain BCL2/Bax-family proteins: mechanisms, physiological roles, and therapeutic opportunities. Cell Death Differ. 2006;13:1378–1386
  6. Konopleva M, Tari AM, Estrov Z, et al. Liposomal BCL2 antisense oligonucleotides enhance proliferation, sensitize acute myeloid leukemia to cytosine-arabinoside, and induce apoptosis independent of other antiapoptotic proteins. Blood. 2000;95:3929–3938
  7. Hu Y, Bebb G, Tan S, et al. Antitumor efficacy of oblimersen BCL2 antisense oligonucleotide alone and in combination with vinorelbine in xenograft models of human non-small cell lung cancer. Clinical Cancer Research. 2004;10:7662–7670
  8. O'Brien S, Moore JO, Boyd TE, et al. Randomized phase III trial of fludarabine plus cyclophosphamide with or without oblimersen sodium (BCL2 antisense) in patients with relapsed or refractory chronic lymphocytic leukemia. Journal of Clinical Oncology. 2007;25:1114–1120
  9. Trudel S, Li ZH, Rauw J, et al. Preclinical studies of the pan-Bcl inhibitor obatoclax (GX015-070) in multiple myeloma. Blood. 2007;109:5430–5438
  10. Shore GC, Viallet J. Modulating the BCL2 family of apoptosis suppressors for potential therapeutic benefit in cancer. Hematology. American Society of Hematology. Education Program. 2005;226–230
  11. Perez-Galan P, Roue G, Villamor N, et al. The BH3-mimetic GX15-070 synergizes with bortezomib in mantle cell lymphoma by enhancing Noxa-mediated activation of Bak. Blood. 2007;109:4441–4449
  12. Borthakur G, O'Brien S, Ravandi-Kashani F, et al. A phase I trial of the small molecule pan-BCL2 family inhibitor obatoclax mesylate (GX15-070) administered by 24 hour infusion every 2 weeks to patients with myeloid malignancies and chronic lymphocytic leukemia (CLL). Blood. 2006;108:751a;(abstr 2654)
  13. Oltersdorf T, Elmore SW, Shoemaker AR, et al. An inhibitor of BCL2 family proteins induces regression of solid tumours. Nature. 2005;435:677–681
  14. Wilkinson JC, Cepero E, Boise LH, et al. Upstream regulatory role for XIAP in receptor-mediated apoptosis. Molecluar and Cellular Biology. 2004;24:7003–7014
  15. Berezovskaya O, Schimmer AD, Glinskii AB, et al. Increased expression of apoptosis inhibitor protein XIAP contributes to anoikis resistance of circulating human prostate cancer metastasis precursor cells. Cancer Research. 2005;65:2378–2386
  16. Tong QS, Zheng LD, Wang L, et al. Downregulation of XIAP expression induces apoptosis and enhances chemotherapeutic sensitivity in human gastric cancer cells. Cancer Gene Therapy. 2005;12:509–514
  17. Tamm I, Richter S, Scholz F, et al. XIAP expression correlates with monocytic differentiation in adult de novo AML: impact on prognosis. The Hematology Journal. 2004;5:489–495
  18. Tamm I, Richter S, Oltersdorf D, et al. High expression levels of x-linked inhibitor of apoptosis protein and survivin correlate with poor overall survival in childhood de novo acute myeloid leukemia. Clinical Cancer Research. 2004;10:3737–3744
  19. Ranson M, Dive C, Ward T, et al. A phase I trial of AEG35156 (XIAP antisense) administered as a 7-day continuous intravenous infusion in patients with advanced tumors. Molecular Targets and Cancer Therapeutics. 2005;215;(abstr C72)
  20. Sun H, Nikolovska-Coleska Z, Yang CY, et al. Structure-based design, synthesis, and evaluation of conformationally constrained mimetics of the second mitochondria-derived activator of caspase that target the X-linked inhibitor of apoptosis protein/caspase-9 interaction site. Journal of Medicinal Chemistry. 2004;47:4147–4150
  21. Sun H, Nikolovska-Coleska Z, Yang CY, et al. Structure-based design of potent, conformationally constrained Smac mimetics. Journal of the American Chemical Society. 2004;126:16686–16687
  22. Nikolovska-Coleska Z, Xu L, Hu Z, et al. Discovery of embelin as a cell-permeable, small-molecular weight inhibitor of XIAP through structure-based computational screening of a traditional herbal medicine three-dimensional structure database. Journal of Medicinal Chemistry. 2004;47:2430–2440
  23. Li L, Thomas RM, Suzuki H, et al. A small molecule Smac mimic potentiates T. Science. 2004;305:1471–1474
  24. Wu TY, Wagner KW, Bursulaya B, et al. Development and characterization of nonpeptidic small molecule inhibitors of the XIAP/caspase-3 interaction. Chemistry & Biology. 2003;10:759–767
  25. Schimmer AD, Welsh K, Pinilla C, et al. Small-molecule antagonists of apoptosis suppressor XIAP exhibit broad antitumor activity. Cancer Cell. 2004;5:25–35
  26. Wang Z, Cuddy M, Samuel T, et al. Cellular, biochemical, and genetic analysis of mechanism of small molecule IAP inhibitors. The Journal of Biological Chemistry. 2004;279:48168–48176
  27. Carter BZ, Gronda M, Wang Z, et al. Small-molecule XIAP inhibitors derepress downstream effector caspases and induce apoptosis of acute myeloid leukemia cells. Blood. 2005;105:4043–4050

☆ This work was supported by the Canadian Institutes of Health Research (CIHR), and the Canadian Cancer Society. A.D.S. is the recipient of a CIHR Clinician Scientist Award.

PII: S1521-6926(07)00091-6

doi: 10.1016/j.beha.2007.11.002

Best Practice & Research Clinical Haematology
Volume 21, Issue 1 , Pages 5-11 , March 2008

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