Role of the Phosphorylation of mTOR in the Differentiation of AML Cells Triggered with CD44 Antigen

Handle URI:
http://hdl.handle.net/10754/293659
Title:
Role of the Phosphorylation of mTOR in the Differentiation of AML Cells Triggered with CD44 Antigen
Authors:
Darwish, Manar M
Abstract:
Acute myeloid leukemia (AML) is a hematological disorder characterized by blockage of differentiation of myeloblasts. To date, the main therapy for AML is chemotherapy. Yet, studies are seeking a better treatment to enhance the survival rate of patients and minimize the relapsing of the disease. Since the major problem in these cells is that they are arrested in cellular differentiation, drugs that could induce their differentiation have proven to be efficient and of major interest for AML therapy. CD44 triggering appeared as a promising target for AML therapy as it has been shown that specific monoclonal antibodies, such as A3D8 and H90, reversed the blockage of differentiation, inhibited the proliferation of all AML subtypes, and in some cases, induced cell apoptosis. Studies conducted in our laboratory have added strength to these antibodies as potential treatment for AML. Indeed, our laboratory found that treating HL60 cells with A3D8 shows a decrease in the phosphorylation of the mammalian target of Rapamycin (mTOR) kinase correlated with the inhibition of proliferation/induction of differentiation of AML cells.The relationship between the induction of differentiation and the inhibition of proliferation and the decrease of mTOR phosphorylation remains to be clarified. To study the importance of the de-phosphorylation of mTOR and the observed effect of CD44 triggering on differentiation and/or proliferation, we sought to prepare phospho-mimic mutants of the mTOR kinase that will code for a constitutively phosphorylated form of mTOR and used two main methods to express this mutant in HL60 cells: lentiviral and simple transfection (cationic-liposomal transfection).
Advisors:
Merzaban, Jasmeen ( 0000-0002-7276-2907 )
Committee Member:
Gadhoum, Samah Z.; Xiong, Liming ( 0000-0001-8099-0806 )
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division
Program:
Bioscience
Issue Date:
May-2013
Type:
Thesis
Appears in Collections:
Bioscience Program; Theses; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.advisorMerzaban, Jasmeenen
dc.contributor.authorDarwish, Manar Men
dc.date.accessioned2013-06-08T11:30:55Z-
dc.date.available2013-06-08T11:30:55Z-
dc.date.issued2013-05en
dc.identifier.urihttp://hdl.handle.net/10754/293659en
dc.description.abstractAcute myeloid leukemia (AML) is a hematological disorder characterized by blockage of differentiation of myeloblasts. To date, the main therapy for AML is chemotherapy. Yet, studies are seeking a better treatment to enhance the survival rate of patients and minimize the relapsing of the disease. Since the major problem in these cells is that they are arrested in cellular differentiation, drugs that could induce their differentiation have proven to be efficient and of major interest for AML therapy. CD44 triggering appeared as a promising target for AML therapy as it has been shown that specific monoclonal antibodies, such as A3D8 and H90, reversed the blockage of differentiation, inhibited the proliferation of all AML subtypes, and in some cases, induced cell apoptosis. Studies conducted in our laboratory have added strength to these antibodies as potential treatment for AML. Indeed, our laboratory found that treating HL60 cells with A3D8 shows a decrease in the phosphorylation of the mammalian target of Rapamycin (mTOR) kinase correlated with the inhibition of proliferation/induction of differentiation of AML cells.The relationship between the induction of differentiation and the inhibition of proliferation and the decrease of mTOR phosphorylation remains to be clarified. To study the importance of the de-phosphorylation of mTOR and the observed effect of CD44 triggering on differentiation and/or proliferation, we sought to prepare phospho-mimic mutants of the mTOR kinase that will code for a constitutively phosphorylated form of mTOR and used two main methods to express this mutant in HL60 cells: lentiviral and simple transfection (cationic-liposomal transfection).en
dc.language.isoenen
dc.subjectmTORen
dc.subjectPhosphorylationen
dc.subjectDifferentiationen
dc.subjectAMLen
dc.subjectCD44en
dc.subjectAntigenen
dc.titleRole of the Phosphorylation of mTOR in the Differentiation of AML Cells Triggered with CD44 Antigenen
dc.typeThesisen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
thesis.degree.grantorKing Abdullah University of Science and Technologyen_GB
dc.contributor.committeememberGadhoum, Samah Z.en
dc.contributor.committeememberXiong, Limingen
thesis.degree.disciplineBioscienceen
thesis.degree.nameMaster of Scienceen
dc.person.id118416en
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