WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

Permanent URI for this collectionhttps://hdl.handle.net/11147/7150

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Institution Author: search.filters.institutionAuthor.Baran, YusufPublisher: search.filters.publisher.American Society of Hematology

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Now showing 1 - 3 of 3
  • Conference Object
    Citation - WoS: 1
    A Study of Multiple Drug Resistance Mechanisms Improved Against Bortezomib on Multiple Myeloma Cell Lines in Vitro
    (American Society of Hematology, 2007) Uyuklu, Tolga; Ural, A. Uğur; Sarper, Metal; Avcu, Ferit; Baran, Yusuf; Elçi, Pınar; Akar, Nejat
    The most important problem in the treatment of Multiple Myeloma (MM) is the multi drug resistance (MDR) observed before and after the treatment. For this reason in MM cases an early resistance to treatment can be developed or the disease can relapsed in early period. Yet, there has been no improved drug resistance against proteazom inhibitor Bortezomib (Bor), which is used alone or with other chemotherapeutic agents in resistant or relapsed MM cases
  • Conference Object
    Autophagic and Apoptotic Effects of Tyrosine Kinase Inhibitors in Myeloid Leukemia: Comparison of Three Generation
    (American Society of Hematology, 2012) Kayabaşı, Çağla; Avcı, Çığır Biray; Süslüer, Sunde Yılmaz; Balcı, Tuğçe; Baran, Yusuf; Saydam, Güray; Gündüz, Cumhur
    [No abstract available]
  • Article
    Citation - WoS: 108
    Citation - Scopus: 119
    Sphingosine Kinase-1 and Sphingosine 1-Phosphate Receptor 2 Mediate Bcr-Abl1 Stability and Drug Resistance by Modulation of Protein Phosphatase 2a
    (American Society of Hematology, 2011) Salas, Arelis; Ponnusamy, Suriyan; Senkal, Can E.; Meyers-Needham, Marisa; Selvam, Shanmugam Panneer; Saddoughi, Sahar A.; Apohan, Elif; Sentelle, R. David; Smith, Charles; Gault, Christopher R.; Obeid, Lina M.; El-Shewy, Hesham M.; Oaks, Joshua; Santhanam, Ramasamy; Marcucci, Guido; Baran, Yusuf; Mahajan, Sandeep; Fernandes, Daniel; Stuart, Robert; Perrotti, Danilo; Öğretmen, Besim
    The mechanisms by which sphingosine kinase-1 (SK-1)/sphingosine 1-phosphate (S1P) activation contributes to imatinib resistance in chronic myeloid leukemia (CML) are unknown. We show herein that increased SK-1/S1P enhances Bcr-Abl1 protein stability, through inhibition of its proteasomal degradation in imatinib-resistant K562/IMA-3 and LAMA-4/IMA human CML cells. In fact, Bcr-Abl1 stability was enhanced by ectopic SK-1 expression. Conversely, siRNA-mediated SK-1 knockdown in K562/IMA-3 cells, or its genetic loss in SK-1-/- MEFs, significantly reduced Bcr-Abl1 stability. Regulation of Bcr-Abl1 by SK-1/S1P was dependent on S1P receptor 2 (S1P2) signaling, which prevented Bcr-Abl1 dephosphorylation, and degradation via inhibition of PP2A. Molecular or pharmacologic interference with SK-1/S1P2 restored PP2A-dependent Bcr-Abl1 dephosphorylation, and enhanced imatinib- or nilotinib-induced growth inhibition in primary CD34+ mononuclear cells obtained from chronic phase and blast crisis CML patients, K562/IMA-3 or LAMA4/IMA cells, and 32Dcl3 murine progenitor cells, expressing the wild-type or mutant (Y253H or T315I) Bcr-Abl1 in situ. Accordingly, impaired SK-1/S1P2 signaling enhanced the growth-inhibitory effects of nilotinib against 32D/T315I-Bcr-Abl1-derived mouse allografts. Since SK-1/S1P/S1P2 signaling regulates Bcr-Abl1 stability via modulation of PP2A, inhibition of SK-1/S1P2 axis represents a novel approach to target wild-type- or mutant-Bcr-Abl1 thereby overcoming drug resistance. © 2011 by The American Society of Hematology.