Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
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Article Citation - WoS: 139Granulocytic Sarcoma: a Systematic Review(e-Century Publishing Corporation, 2013) Yılmaz, Asu Fergün; Saydam, Güray; Şahin, Fahri; Baran, YusufGranulocytic sarcoma also called myeloid sarcoma is an extramedullary tumor of immature granulocytic cells. It is a rare entity, and mostly accompanied by acute myeloid leukemia. It is observed during the course of myeloproliferative disorders especially in chronic myeloid leukemia and myelodysplastic syndromes. In some rare circumstances, it is detected before clinical signs of leukemia or other diseases. When the bone marrow biopsy reveals no other hematologic malignancies, the granulocytic sarcoma is described as nonleukemic, primary or isolated. It is observed at any part of the body but the most common locations are soft tissues, bone, peritoneum and lymph nodes. Presenting signs or symptoms are mainly due to mass effect of the tumor and dysfunction of the organ, or the tissue that is affected. The diagnosis is performed by biopsy of the tumor. The tumor consists of immature granulocytic cells, which could be documented by H&E, immunohistochemistry, and flow cytometric methods. Fluorescence in-situ hybridization and molecular analysis are also performed. The optimal time and type of treatment is not clear. Surgery could be an option especially for tumors, which cause organ dysfunction and/or obstruction. Systemic treatment should be considered in all patients because without systemic treatment, relapses and progression to acute myeloid leukemia is the ultimate fate of the disease in many cases. Cytarabine-containing remission-induction chemotherapies have been the most applied therapeutic strategies, but it is not clear whether the consolidation therapies are required or not, and what kind of regimens are appropriate. The role of hematopoietic stem cell transplantation (HSC) as a consolidation regimen is not clear, but, after the relapse of the disease with or without bone marrow involvement, HSC transplantation should be considered in suitable patients after the reinduction performed by AML chemotherapies. There is only limited data about the role of radiotherapy in these patients. It could be used in patients with relapsed disease, organ dysfunction which should be quickly relieved and inadequate response to chemotherapy. The effect of radiotherapy on overall survival is not known. New prospective studies and clinical trials are needed to generate guidelines for the treatment of primary granulocytic sarcomas.Article Citation - WoS: 15Changes in Molecular Biology of Chronic Myeloid Leukemia in Tyrosine Kinase Inhibitor Era(e-Century Publishing Corporation, 2013) Cömert, Melda; Baran, Yusuf; Saydam, GürayChronic myeloid leukemia (CML) is a clonal myeloproliferative disease characterized by a reciprocal translocation between long arms of chromosomes 9 and 22 t(9; 22) that generates the BCR-ABL fusion gene. If left untreated, newly diagnosed chronic phase CML patients finally progress to accelerated and blastic phase. After the introduction of tyrosine kinase inhibitors (TKIs), treatment strategies of CML changed dramatically. However, the development of resistance to TKIs started to create problems over time. In this review, the current information about CML biology before and after imatinib mesylate treatment is summarized.Article Citation - WoS: 16Cumulative Clinical Experience From a Decade of Use: Imatinib as First-Line Treatment of Chronic Myeloid Leukemia(Dove Medical Press Ltd., 2012) Baran, Yusuf; Saydam, GürayChronic myeloid leukemia (CML) is a malignant disease that originates in the bone marrow and is designated by the presence of the Philadelphia (Ph+) chromosome, a translocation between chromosomes 9 and 22. Targeted therapy against CML commenced with the development of small-molecule tyrosine kinase inhibitors (TKIs) exerting their effect against the oncogenic breakpoint cluster region (BCR)-ABL fusion protein. Imatinib emerged as the first successful example of a TKI used for the treatment of chronic-phase CML patients and resulted in significant improvements in response rate and overall survival compared with previous treatments. However, a significant portion of patients failed to respond to the therapy and developed resistance against imatinib. Second-generation TKIs nilotinib and dasatinib were to have higher efficiency in clinical trials in imatinib- resistant or intolerant CML patients com pared with imatinib. Identification of novel strategies such as dose escalation, drug combination therapy, and use of novel BCR-ABL inhibitors may eventually overcome resistance against BCR-ABL TKIs. This article reviews the history of CML, including the treatment strategies used prediscovery of TKIs and the preclinical and clinical data obtained after the use of imatinib, and the second-generation TKIs developed for the treatment of CML.Conference Object Expression Levels of Jak/Stat Signaling Genes in Newly Diagnosed, Drug Sensitive and Resistant Chronic Myeloid Leukemia Patients(Ferrata Storti Foundation, 2015) Kiraz, Yağmur; Saydam, Güray; Şahin, Fahri; Kozanoğlu, İlknur; Özdoğu, Hakan; Pişkin, Özden; Baran, Yusuf[No abstract available]Article Citation - WoS: 10Citation - Scopus: 14Enalapril-Induced Apoptosis of Acute Promyelocytic Leukaemia Cells Involves Stat5a(International Institute of Anticancer Research, 2012) Purçlutepe, Özlem; İskender, Güniz; Kiper, Hatice Demet; Tezcanlı, Burçin; Selvi, Nur; Biray Avcı, Çığır; Kosova, Buket; Adan Gökbulut, Aysun; Şahin, Fahri; Baran, Yusuf; Saydam, GürayBackground: In this study, we aimed at evaluating the cytotoxic and apoptotic effects of enalapril on human HL60 acute promyelocytic leukaemia cells and at clarifying the roles of signal transducers and activator of transcription proteins (STATs) on enalapril-induced cell death. Materials and Methods: Cell viability and cytotoxicity tests were conducted by Trypan blue dye exclusion and 2,3-Bis[2-methoxy-4-nitro-5-sulphophenyl]-2H-tetrazolium-5- carboxanilide inner salt (XTT) assays, respectively. Apoptotic analyses were performed by the AnnexinV-enhanced green fluorescent protein (EGFP) staining method and by fluorescence microscopy. Expression levels of STAT3, -5A and -5B genes were analysed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Results: The results showed that enalapril reduced viability and proliferation, and induced apoptosis in HL60 cells in a dose-and time-dependent manner as compared to untreated controls. The expression levels of STAT5A gene were significantly reduced in enalapril-treated HL60 cells as compared to untreated controls. Conclusion: Taken together, all data showed for the first time that enalapril has significant anticancer potential for the treatment of acute premyelocytic leukaemia.Article Citation - WoS: 13Citation - Scopus: 13Stat Pathway in the Regulation of Zoledronic Acid-Induced Apoptosis in Chronic Myeloid Leukemia Cells(Elsevier Ltd., 2013) Kiper, Hatice Demet; Tezcanlı Kaymaz, Burçin; Adan Gökbulut, Aysun; Selvi, Nur; Biray Avcı, Çığır; Kosova, Buket; İskender, Güniz; Kartal Yandım, Melis; Gündüz, Cumhur; Şahin, Fahri; Baran, Yusuf; Saydam, GürayIn this study, we aimed to evaluate the cytotoxic and apoptotic effects of zoledronic acid on K562 chronic myeloid leukemia (CML) cells and to examine the roles of STAT genes on zoledronic acid-induced apoptosis. The results showed that zoledronic acid decreased proliferation, and induced apoptosis in K562 cells in a dose- and time-dependent manner. mRNA and protein levels of STAT3, -5A and -5B genes were significantly reduced in zoledronic acid-treated K562 cells. These data indicated that STAT inhibition by zoledronic acid may be therapeutic in CML patients following the confirmation with clinical studies. © 2013 Elsevier Masson SAS.Article Citation - WoS: 36Citation - Scopus: 42Resveratrol Triggers Apoptosis Through Regulating Ceramide Metabolizing Genes in Human K562 Chronic Myeloid Leukemia Cells(Routledge, 2011) Kartal Yandım, Melis; Saydam, Güray; Şahin, Fahri; Baran, YusufResveratrol, an important phytoalexin in many plants, has been reported to have cytotoxic effects on various types of cancer. Ceramide is a bioactive sphingolipid that regulates many signaling pathways, including cell growth and proliferation, senescence and quiescence, apoptosis, and cell cycle. Ceramides are generated by longevity assurance genes (LASS). Glucosylceramide synthase (GCS) and sphingosine kinase-1 (SK-1) enzymes can convert ceramides to antiapoptotic molecules, glucosylceramide, and sphingosine-1-phosphate, respectively. C8:ceramide, an important cell-permeable analogue of natural ceramides, increases intracellular ceramide levels significantly, while 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) and SK-1 inhibitor increase accumulation of ceramides by inhibiting GCS and SK-1, respectively. Chronic myelogenous leukemia (CML) is a hematological disorder resulting from generation of BCR/ABL oncogene. In this study, we examined the roles of ceramide metabolizing genes in resveratrol-induced apoptosis in K562 CML cells. There were synergistic cytotoxic and apoptotic effects of resveratrol with coadministration of C8:ceramide, PDMP, and SK-1 inhibitor. Interestingly, there were also significant increases in expression levels of LASS genes and decreases in expression levels of GCS and SK-1 in K562 cells in response to resveratrol. Our data, in total, showed for the first time that resveratrol might kill CML cells through increasing intracellular generation and accumulation of apoptotic ceramides. Copyright © 2011, Taylor & Francis Group, LLC.Article Citation - WoS: 31Citation - Scopus: 36Quercetin-Induced Apoptosis Involves Increased Htert Enzyme Activity of Leukemic Cells(Taylor and Francis Ltd., 2011) Avcı, Çığır Biray; Yılmaz, Sunde; Doğan, Zeynep Özlem; Saydam, Güray; Dodurga, Yavuz; Ekiz, Hüseyin Atakan; Kartal, Melis; Şahin, Fahri; Baran, Yusuf; Gündüz, CumhurWe aimed to examine the growth suppressive effects of quercetin on acute promyelocytic and lymphoblastic leukemia and chronic myeloid leukemia, and to find out whether the growth suppression is related to the blocking of telomerase enzyme activity. Cytotoxic effects of quercetin were shown by trypan blue analyses. Apoptotic effects of quercetin were examined by acridine orange and ethidium bromide staining by fluorescence microscopy. The effects of quercetin on telomerase enzyme activity were shown by hTERT Quantification Kit. Our results demonstrated that quercetin has antiproliferative and apoptotic effects on T-cell acute lymphoblastic leukemia (ALL), acute promyelocytic leukemia, and chronic myeloid leukemia (CML) cells. We also showed for the first time by this study that quercetin suppresses the activity of telomerase in ALL and CML cells. The results of this study show the importance of quercetin for its therapeutic potential in treatment of leukemias.Article Citation - WoS: 22Citation - Scopus: 28Caffeic Acid Phenethyl Ester Triggers Apoptosis Through Induction of Loss of Mitochondrial Membrane Potential in Ccrf-Cem Cells(Springer Verlag, 2011) Avcı, Çığır Biray; Gündüz, Cumhur; Baran, Yusuf; Şahin, Fahri; Yılmaz, Sunde; Doğan, Zeynep Özlem; Saydam, GürayPurpose CAPE (caffeic acid phenethyl ester) is one of the most valuable and investigated component of propolis which is composed by honeybees. In the current study, we aimed at examining apoptotic effects of CAPE on CCRF-CEM leukemic cells and at determining the roles of mitochondrial membrane potential (MMP) in cell death. Methods Trypan blue and XTT methods were used to evaluate the cytotoxicity. Apoptosis was examined by ELISA-based oligonucleotide and acridine orange/ethidium bromide dye techniques. Loss of mitochondrial membrane potential was evaluated using JC-1 dye by flow cytometric analysis and under fluorescent microscope. Results We detected the time-and dose-dependent increases in cytotoxic effect of CAPE on CCRF-CEM cells. ELISA and acridine orange/ethidium bromide results showed that apoptotic cell population increased significantly in CCRF-CEM cells exposed to increasing concentrations of CAPE. On the other hand, there was significant loss of MMP determined in response to CAPE in CCRF-CEM cells. Conclusion This in vitro data by being supported with clinical data may open the way of the potential use of CAPE for the treatment of leukemia.