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XIE Weiquan, DAI Wen, WANG Shuzhen, CHEN Yijun. A novel peptide and its mechanism overcoming imatinib-resistance chronic myeloid leukemia[J]. Journal of China Pharmaceutical University, 2014, 45(3): 368-372. DOI: 10.11665/j.issn.1000-5048.20140321
Citation: XIE Weiquan, DAI Wen, WANG Shuzhen, CHEN Yijun. A novel peptide and its mechanism overcoming imatinib-resistance chronic myeloid leukemia[J]. Journal of China Pharmaceutical University, 2014, 45(3): 368-372. DOI: 10.11665/j.issn.1000-5048.20140321
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A novel peptide and its mechanism overcoming imatinib-resistance chronic myeloid leukemia

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    • Abstract
  • COG133, a peptide inhibitor of SET, can enhance PP2A activity to treat imatinib-resistant CML by T315I mutation. Based on this fact, a peptide designated as SP2 showed the best anti-tumor activity among nine newly-designed Apolipoprotein E-mimetic peptides compared to COG133. The IC50 of SP2 against BaF3-p-210(T315I)cells was(2. 9±0. 1)μmol/L at 72 h, 10% of that of COG133(26. 5±1. 2 μmol/L). Further studies indicated that SP2 antagonizes SET protein to increase the activity of PP2A, thereby dephosphorylating p-BCR-ABL to induce cell apoptosis.
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    • References (19)
  • [1]
    Deininger M,Buchdunger E,Druker BJ,et al.The development of imatinib as a therapeutic agent for chronic myeloid leukemia[J].Blood,2005,105(7):2 640-2 653.
    [2]
    Buchdunger E,Matter A,Druker BJ,et al.Bcr-Abl inhibition as a modality of CML therapeutics[J].BiochimBiophys Acta,2001,1 551(1):1-11.
    [3]
    Sawyers CL,Hochhaus A,Feldman E,et al.Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis:results of a phase II study[J].Blood,2002,99(10):3 530-3 539.
    [4]
    Ottmann OG,Druker BJ,Sawyers CL,et al.A phase 2 study of imatinib in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoid leukemia[J].Blood,2002,100(6):1 965-1 971.
    [5]
    Gorre ME,Mohammed M,Ellwood K,et al.Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification[J].Science,2001,293(5531):876-880.
    [6]
    Shah NP,Tran C,Lee FY,et al.Overriding imatinib resistance with a novel ABL kinase inhibitor[J].Science,2004,305(5 682):399-401.
    [7]
    Weisberg E,Manley PW,Breitenstein W,et al.Characterization of AMN107,a selective inhibitor of native and mutant Bcr-Abl[J].Cancer cell,2005,7(2):129-141.
    [8]
    Cortes JE,Kantarjian H,Shah NP,et al.Ponatinib in refractory Philadelphia chromosome-positive leukemias[J].N Engl J Med,2012,367(22):2 075-2 088.
    [9]
    Khorashad JS,Kelley TW,Szankasi P,et al.BCR-ABL1 compound mutations in tyrosine kinase inhibitor-resistant CML:frequency and clonal relationship[J].Blood,2013,121(3):489-498.
    [10]
    Perrotti D,Neviani P.Resetting PP2A tumour suppressor activity in blast crisis and imatinib-resistant chronic myelogenous leukemia[J].Br J Cancer,2006,95(7):775-781.
    [11]
    Neviani P,Santhanam R,Trotta R,et al.The tumor suppressor PP2A is functionally inactivated in blast crisis CML through the inhibitory activity of the BCR/ABL-regulated SET protein[J].Cancer cell,2005,8(5):355-368.
    [12]
    Christensen DJ,Chen Y,Oddo J,et al.SET oncoprotein overexpression in B-cell chronic lymphocytic leukemia and non-Hodgkin lymphoma:a predictor of aggressive disease and a new treatment target[J].Blood,2011,118(15):4 150-4 158.
    [13]
    Yang Y,Huang Q,Lu Y,et al.Reactivating PP2A by FTY720 as a novel therapy for AML with C-KIT tyrosine kinase domain mutation[J].J Cell Biochem,2012,113(4):1 314-1 322.
    [14]
    Saddoughi SA,Gencer S,Peterson YK,et al.Sphingosine analogue drug FTY720 targets I2PP2A/SET and mediates lung tumour suppression via activation of PP2A-RIPK1-dependent necroptosis[J].EMBO Mol Med,2013,5(1):105-121.
    [15]
    Cristobal I,Garcia-Orti L,Cirauqui C,et al.PP2A impaired activity is a common event in acute myeloid leukemia and its activation by forskolin has a potent anti-leukemic effect[J].Leukemia,2011,25(4):606-614.
    [16]
    Mukhopadhyay A,Saddoughil SA,Song P,et al.Direct interaction between the inhibitor 2 and ceramid via sphingolipid-protein binding is involved in the regulation of protein phosphatase 2A activity and signaling[J].FASEB J,2009,23(3):755-763.
    　　    [17] Christensen DJ,Ohkubo N,Oddo J,et al.Apolipoprotein E and peptide mimetics modulate inflammation by binding the SET protein and activating protein phosphatase 2A[J].J Immunol,2011,186(4):2 535-2 542.
    [17]
    Switzer CH,Cheng RY,Vitek TM,et al.Targeting SET/I2PP2A oncoprotein functions as a multi-pathway strategy for cancer therapy[J].Oncogene,2011,30(22):2 504-2 513.
    [18]
    Switzer CH,Cheng RY,Vitek TM,et al.Antagonism of SET using OP449 enhances the efficacy of tyrosine kinase inhibitors and overcomes drug resistance in myeloid leukemia[J].Clin Cancer Res,2014,20(8):2 092-2 103.
    [19]
    Tukhovskaya EA,Yukin AY,Khokhlova ON,et al.COG1410,a novel apolipoprotein-E mimetic,improves functional and morphological recovery in a rat model of focal brain ischemia[J].J Neurosci Res,2009,87(3):677-682.
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