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Effective targeting of chronic myeloid leukemia initiating activity with the combination of arsenic trioxide and interferon alpha

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dc.contributor.author El Eit R.M.
dc.contributor.author Iskandarani A.N.
dc.contributor.author Saliba J.L.
dc.contributor.author Jabbour M.N.
dc.contributor.author Mahfouz R.A.
dc.contributor.author Bitar N.M.A.
dc.contributor.author El Ayoubi H.R.
dc.contributor.author Zaatari G.S.
dc.contributor.author Mahon F.-X.
dc.contributor.author De The H.B.
dc.contributor.author Bazarbachi A.A.
dc.contributor.author Nasr R.R.
dc.contributor.editor
dc.date Feb-2014
dc.date.accessioned 2017-10-05T15:59:39Z
dc.date.available 2017-10-05T15:59:39Z
dc.date.issued 2014
dc.identifier 10.1002/ijc.28427
dc.identifier.isbn
dc.identifier.issn 00207136
dc.identifier.uri http://hdl.handle.net/10938/19139
dc.description.abstract Imatinib is the standard of care in chronic meloid leukemia (CML) therapy. However, imatinib is not curative since most patients who discontinue therapy relapse indicating that leukemia initiating cells (LIC) are resistant. Interferon alpha (IFN) induces hematologic and cytogenetic remissions and interestingly, improved outcome was reported with the combination of interferon and imatinib. Arsenic trioxide was suggested to decrease CML LIC. We investigated the effects of arsenic and IFN on human CML cell lines or primary cells and the bone marrow retroviral transduction-transplantation murine CML model. In vitro, the combination of arsenic and IFN inhibited proliferation and activated apoptosis. Importantly, arsenic and IFN synergistically reduced the clonogenic activity of primary bone marrow cells derived from CML patients. Finally, in vivo, combined interferon and arsenic treatment, but not single agents, prolonged the survival of primary CML mice. Importantly, the combination severely impaired engraftment into untreated secondary recipients, with some recipients never developing the disease, demonstrating a dramatic decrease in CML LIC activity. Arsenic-IFN effect on CML LIC activity was significantly superior to that of imatinib. These results support further exploration of this combination, alone or with imatinib aiming at achieving CML eradication rather than long-term disease control. What's new? The tyrosine kinase inhibitor imatinib has become the standard therapy for Chronic Myeloid Leukemia (CML). However, imatinib is not curative since most patients who discontinue therapy relapse, indicating that leukemia initiating cells are resistant. Here the authors demonstrated that arsenic and interferon alpha (IFN) inhibited the clonogenic activity of human primary CML cells. In a murine CML model, arsenic-IFN sharply diminished transplantation of CML cells, pointing to exhaustion of CML initiating cells. These studies plea for clinical exploration of this combination, knowing that IFN and arsenic have both previously shown clinical activity in CML, alone or in combination with imatinib. © 2013 UICC.
dc.format.extent
dc.format.extent Pages: (988-996)
dc.language English
dc.publisher HOBOKEN
dc.relation.ispartof Publication Name: International Journal of Cancer; Publication Year: 2014; Volume: 134; no. 4; Pages: (988-996);
dc.relation.ispartofseries
dc.relation.uri
dc.source Scopus
dc.subject.other
dc.title Effective targeting of chronic myeloid leukemia initiating activity with the combination of arsenic trioxide and interferon alpha
dc.type Article
dc.contributor.affiliation El Eit, R.M., Department of Anatomy, Cell Biology and Physiology, American University of Beirut, Beirut 1107 2020, Lebanon
dc.contributor.affiliation Iskandarani, A.N., Department of Anatomy, Cell Biology and Physiology, American University of Beirut, Beirut 1107 2020, Lebanon
dc.contributor.affiliation Saliba, J.L., Department of Anatomy, Cell Biology and Physiology, American University of Beirut, Beirut 1107 2020, Lebanon
dc.contributor.affiliation Jabbour, M.N., Department of Pathology and Laboratory Medicine, American University of Beirut, Beirut, Lebanon
dc.contributor.affiliation Mahfouz, R.A., Department of Pathology and Laboratory Medicine, American University of Beirut, Beirut, Lebanon
dc.contributor.affiliation Bitar, N.M.A., Hematology-Oncology Internal Medicine Lebanese University, Faculty of Medical Sciences, Sahel General Hospital, Beirut, Lebanon
dc.contributor.affiliation El Ayoubi, H.R., Hamad Medical Corporation, Doha, Qatar
dc.contributor.affiliation Zaatari, G.S., Department of Pathology and Laboratory Medicine, American University of Beirut, Beirut, Lebanon
dc.contributor.affiliation Mahon, F.-X., Laboratoire d'Hématologie et Service des Maladies du Sang, CHU de Bordeaux, Université Victor Ségalen Bordeaux 2, Bordeaux, France
dc.contributor.affiliation De Thé, H.B., Service de Biochimie, CNRS-INSERM-Université Paris Diderot UMR 7212, Hôpital Saint Louis, Paris, France
dc.contributor.affiliation Bazarbachi, A.A., Department of Anatomy, Cell Biology and Physiology, American University of Beirut, Beirut 1107 2020, Lebanon, Department of Internal Medicine, American University of Beirut, Beirut, Lebanon
dc.contributor.affiliation Nasr, R.R., Department of Anatomy, Cell Biology and Physiology, American University of Beirut, Beirut 1107 2020, Lebanon
dc.contributor.authorAddress Nasr, R.R.; Department of Anatomy, Cell Biology and Physiology, American University of Beirut, Beirut 1107 2020, Lebanon; email: rn03@aub.edu.lb
dc.contributor.authorCorporate University: American University of Beirut Medical Center; Faculty: Faculty of Medicine; Department: Pathology and Laboratory Medicine;
dc.contributor.authorDepartment Pathology and Laboratory Medicine
dc.contributor.authorDivision
dc.contributor.authorEmail rn03@aub.edu.lb
dc.contributor.authorFaculty Faculty of Medicine
dc.contributor.authorInitials El Eit, RM
dc.contributor.authorInitials Iskandarani, AN
dc.contributor.authorInitials Saliba, JL
dc.contributor.authorInitials Jabbour, MN
dc.contributor.authorInitials Mahfouz, RA
dc.contributor.authorInitials Bitar, NMA
dc.contributor.authorInitials El Ayoubi, HR
dc.contributor.authorInitials Zaatari, GS
dc.contributor.authorInitials Mahon, FX
dc.contributor.authorInitials De The, HB
dc.contributor.authorInitials Bazarbachi, AA
dc.contributor.authorInitials Nasr, RR
dc.contributor.authorOrcidID
dc.contributor.authorReprintAddress Nasr, RR (reprint author), Amer Univ Beirut, Dept Anat Cell Biol and Physiol Sci, Beirut 11072020, Lebanon.
dc.contributor.authorResearcherID
dc.contributor.authorUniversity American University of Beirut Medical Center
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dc.description.citedCount 3
dc.description.citedTotWOSCount 5
dc.description.citedWOSCount 5
dc.format.extentCount 9
dc.identifier.articleNo
dc.identifier.coden IJCNA
dc.identifier.pubmedID
dc.identifier.scopusID 84890127013
dc.identifier.url
dc.publisher.address 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
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dc.relation.ispartofConferenceCode
dc.relation.ispartofConferenceDate
dc.relation.ispartofConferenceHosting
dc.relation.ispartofConferenceLoc
dc.relation.ispartofConferenceSponsor
dc.relation.ispartofConferenceTitle
dc.relation.ispartofFundingAgency
dc.relation.ispartOfISOAbbr Int. J. Cancer
dc.relation.ispartOfIssue 4
dc.relation.ispartOfPart
dc.relation.ispartofPubTitle International Journal of Cancer
dc.relation.ispartofPubTitleAbbr Int. J. Cancer
dc.relation.ispartOfSpecialIssue
dc.relation.ispartOfSuppl
dc.relation.ispartOfVolume 134
dc.source.ID WOS:000327889700028
dc.type.publication Journal
dc.subject.otherAuthKeyword arsenic trioxide
dc.subject.otherAuthKeyword chronic myeloid leukemia
dc.subject.otherAuthKeyword CML mouse model
dc.subject.otherAuthKeyword imatinib
dc.subject.otherAuthKeyword interferon alpha
dc.subject.otherAuthKeyword leukemia initiating cells
dc.subject.otherChemCAS arsenic trioxide, 1303-24-8, 1327-53-3, 13464-58-9, 15502-74-6
dc.subject.otherChemCAS imatinib, 152459-95-5, 220127-57-1
dc.subject.otherIndex alpha interferon
dc.subject.otherIndex arsenic trioxide
dc.subject.otherIndex imatinib
dc.subject.otherIndex animal experiment
dc.subject.otherIndex animal model
dc.subject.otherIndex animal tissue
dc.subject.otherIndex apoptosis
dc.subject.otherIndex article
dc.subject.otherIndex bone marrow cell
dc.subject.otherIndex cancer survival
dc.subject.otherIndex cell proliferation
dc.subject.otherIndex chronic myeloid leukemia
dc.subject.otherIndex concentration response
dc.subject.otherIndex controlled study
dc.subject.otherIndex disease severity
dc.subject.otherIndex drug efficacy
dc.subject.otherIndex drug targeting
dc.subject.otherIndex human
dc.subject.otherIndex human cell
dc.subject.otherIndex human tissue
dc.subject.otherIndex in vivo study
dc.subject.otherIndex leukemia initiating cell
dc.subject.otherIndex mouse
dc.subject.otherIndex nonhuman
dc.subject.otherIndex primary cell culture
dc.subject.otherIndex primary tumor
dc.subject.otherIndex priority journal
dc.subject.otherIndex tumor cell line
dc.subject.otherKeywordPlus CHRONIC MYELOGENOUS LEUKEMIA
dc.subject.otherKeywordPlus T-CELL LEUKEMIA-LYMPHOMA
dc.subject.otherKeywordPlus ACUTE PROMYELOCYTIC LEUKEMIA
dc.subject.otherKeywordPlus I-TRANSFORMED-CELLS
dc.subject.otherKeywordPlus BCR-ABL
dc.subject.otherKeywordPlus STEM-CELLS
dc.subject.otherKeywordPlus PHILADELPHIA-CHROMOSOME
dc.subject.otherKeywordPlus POSITIVE LEUKEMIAS
dc.subject.otherKeywordPlus TYROSINE KINASE
dc.subject.otherKeywordPlus IMATINIB
dc.subject.otherWOS Oncology


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