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).
| Identifer | oai:union.ndltd.org:kaust.edu.sa/oai:repository.kaust.edu.sa:10754/293659 |
| Date | 05 1900 |
| Creators | Darwish, Manar M. |
| Contributors | Merzaban, Jasmeen, Biological and Environmental Sciences and Engineering (BESE) Division, Gadhoum, Samah Z., Xiong, Liming |
| Source Sets | King Abdullah University of Science and Technology |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Rights | 2014-05-31, At the time of archiving, the student author of this thesis opted to temporarily restrict access to it. The full text of this thesis became available to the public after the expiration of the embargo on 2014-05-31. |
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