Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 17 of 17 for “"AF9"”.
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The Role of AF9 and AF9-Mediated Protein Interactions in Hematopoiesis and Leukemogenesis
<p>The AF9 protein is one of the most common chromosomal translocation partners of the MLL gene in MLL leukemia. Wild-type AF9 is a member of the pTEFb transcription elongation complex, and interacts with gene regulatory proteins such as AF4/AF5q31, DOT1L, Pc3/CBX8 and BCoR. These interactions are …
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Significance of Protein Interactions in Mediating AF9 Function
… the expression of MLL target genes.</p><p>AF9 is one of the most common MLL fusion partners encountered in patients with leukemias. Moreover, Af9 is known to negatively regulate the expression of the epithelial sodium channel α (ENaCα) gene in murine renal collecting ducts by modulating the …
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Oncogenic roles of RAS in acute myeloid leukemia cooperated with Mll-AF9.
… was developed in Vav-tTA TRE-NRASG12V ; Mll-AF9 transgenic ( TRM -transgenic) mice, into recipient SCID mice. Conditional repression of NRAS G12V expression greatly reduced peripheral white blood cell (WBC) counts in leukemia recipient mice and induced apoptosis in the transplanted AML cells …
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The Specific Role of the MLL CXXC Domain in MLL Fusion Protein Function
… cells expressing mutant or wild type MLL-AF9 fusion proteins. MLL-AF9 containing the DNMT1 CXXC domain showed robust colony forming activity and in vivo leukemogenesis activity, similar to the oncogenic MLL-AF9 fusion. However, MLL-AF9 containing either the CXXC domain from CGBP or MBD1, …
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A Study of the Therapeutic Potential of AF4 Mimetic Peptides
… as a means of inhibiting MLL leukemia. AF4 and AF9 proteins co-purify with components of the SEC and directly interact with each other. Our laboratory has previously identified the domain of AF4 which is required for AF9 interaction and demonstrated that inhibition of this interaction using an …
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Critical Functions Specified by the MLL CXXC Domain Determine Leukemogenic Capacity
… cloned into the context of the well-studied MLL-AF9 fusion protein to generate an artificial MLL/MLL2-AF9 chimera. Amino acid substitutions were then introduced within the MLL2 CXXC domain of this synthetic chimera to restore residues to the MLL sequence. By comparing residues of the MLL and MLL2 …
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Role of S6K1 in regulating self-renewal of hematopoietic stem cells and propagatoin of leukemia
… of acute leukemias in infants. We expressed MLL-AF9 fusion oncoprotein in WT and S6K1-/- hematopoietic stem and progenitor cells (HSC/Ps) and performed serial transplantation. Upon secondary transplantation, recipients of S6K1 deficient AML cells survived significantly longer compared to …
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Mechanistic Insights into Direct Interactions that Mediate the Activity of DOT1L Complex in MLL-Rearranged Leukemia
… have been identified, fusion partners such as AF9, AF10, and ENL constitute the majority of the MLL-rearranged leukemia cases; additionally, these fusion partners are also a part of the DOT1L (disruptor of telomeric silencing 1-like) complex. Aberrant histone H3 Lysine 79 (H3K79) methylation …
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Topology of Genes in Mammalian Cell Nuclei with Special Emphasis on the MLL Gene and Its Translocation Partners
… five of its translocation partners, (AF4, AF6, AF9, ENL and ELL) and four control loci (2q33, 2q35, 7q22 and 8q34) were analyzed in different human cell lines of hematopoietic origin and in primary hematopoietic stem cells. Despite the cell materials’ differences in maturation state, cell …
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Investigating the translational and metabolic reprogramming of the bone marrow niche in myeloid malignancy
… of highly chemo-resistant AML driven by MLL-AF9 or FLT3-ITD;NPMc mutations, we show that AML protein synthesis levels increase at relapse dependently on nestin+ BMSCs. Inhibiting cap-dependent translation in BMSCs abolishes their chemoprotective ability, whereas BMSCs and their EVs rescue …
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The Cell-Essentiality of KAT7 in Acute Myeloid Leukemia
… are critical for the maintenance of the MLL-AF9 transcriptional programme. Although not found to be mutated among cases of AML, KAT7 is a plausible therapeutic target for this poor prognosis subtype of AML.
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Trim24 In Normal & Malignant Hematopoiesis
… of <em>Trim24</em> in murine, <em>MLL</em>-<em>AF9</em>-driven AML worsened survival and increased leukemic stem cell numbers, while having no observed effects on normal hematopoiesis. These results lay the groundwork for future investigations of the role of <em>TRIM24</em> in AML, which has the …
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Cold Shock Domain Proteins in Normal and Leukemic Hematopoiesis
… both proteins leads to a reduced ability for MLL-AF9 (a potent leukemia-initiating gene) expressing bone marrow cells to proliferate and serially replate in vitro, suggesting that Ybx1 and Msy4 have redundant functions in this model system. Since these proteins are involved in the prevention of …
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Role of DDX RNA helicases in cancer cells
… dropout screen in a leukaemia cell line (MLL-AF9) showed that both helicases are essential for growth of these cells. However, loss of DDX3X or DDX54 had little effect on proliferation of immortalized NIH3T3 cells indicating that their loss is not generally lethal. In subsequent CRISPR/Cas9 …
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Metabolic Regulation of Gene Expression through Differential Histone Acylation: The Regulation and Function of Histone Crotonylation
… and genetic studies we showed that AF9 and the YEATS-Kcr interaction is responsible for the enhanced expression of increased Kcr. This work is discussed in Chapter 5. As discussed in Chapter 6, I have also identified and characterized several decrotonylase (eraser) activities. The …
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From Mechanisms of Leukaemogenic Dysregulation to New Candidate Therapeutics
… Despite having more than 80 fusion partners, MLL-AF9, MLL-AF4 and MLL-ENL make up more than 60% of cases involving *MLL1* translocations. Conventional retroviral transduction models commonly use lineage depleted or c-Kit enriched mouse bone marrow haematopoietic stem and progenitor cells (HSPCs) …