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 20 of 32 for “"FLT3"”.
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Concomitant Inhibition of Flt3 and Mcl-1 In Flt3 Mutated Acute Myeloid Leukemia
<p>The MCL-1 inhibitor S63845 synergizes with the FLT3 inhibitor midostaurin for potent anti-leukemic effect in preclinical human models of FLT3-ITD mutated acute myeloid leukemia (AML). Acute Myeloid leukemia (AML) is a neoplastic blood disorder defined by a characteristically rapid growth rate …
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Regulation of flt3 gene expression in haematopoietic and leukaemic stem cells
… interaction between the tyrosine kinase receptor Flt3 and its ligand leads to signalling during the commitment of haematopoietic stem cells (HSCs). Constitutive activation of the Flt3/FL pathway is a key factor in enhanced survival and expansion in acute myeloid leukaemia (AML). Although there is …
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Studies on signaling pathways induced by FLT3, an important oncogene in AML
FLT3, a receptor tyrosine kinase, is expressed in hematopoietic progenitor cells. FLT3-ITD (internal tandem duplication) and D835 mutations are found in approximately 30% and 7% of Acute Myeloid Leukemia (AML) patients respectively, and correlate with a poor prognosis, thus making the mutated …
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Targeting the protein tyrosine phosphatase, SHP2, and PI3K in FLT3-ITD+ leukemia
… in the fms-like tyrosine kinase receptor (FLT3-ITDs) cause constitutive activation of the receptor and confer a poor prognosis in acute myeloid leukemia (AML). We hypothesized that Shp2 interacts with FLT3-ITD via protein complexes at tyrosine (Y) 768, 955, and/or 969 and that Shp2 and PI3K …
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T-Regulatory Cells and FLT3-Ligand in the Therapy of Cockroach Antigen-induced Asthma
… of mice that received the anti-PD-1 antagonist.|Flt3-ligand (Flt3-L), a hematopoietic growth factor, dramatically increased the number of dendritic cells in the lungs of Ova-sensitized and challenged mice. Therefore, the effect of Flt3-L on CD4+CD25+ T cells in cockroach-sensitized and challenged …
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Functional Responses of Lung Dendritic Cell Subsets in Flt3 Ligand-Induced Immunomodulation in Allergic Asthma
… towards Th1 or Th2 immunity, or tolerance. Flt3-ligand (Flt3-L) is an indispensible synergistic hematopoietic growth factor for DC development and differentiation in hematopoietic and peripheral lymphoid organs. Administration of Flt3-L specifically affects the generation, phenotype and …
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Redox biology of myeloid leukaemias
… of FMS-like receptor tyrosine kinase (FLT3-ITD) has been associated with an aggressive AML phenotype. FLT3-ITD expressing cell lines have been shown to generate increased levels of reactive oxygen species (ROS) and DNA double strand breaks (dsbs). However, the molecular basis of how …
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Deciphering the Pathogenesis of Acute Myeloid Leukemia
… addition, internal tandem duplications (ITD) of FLT3 are frequently observed alterations in AML and coincide with mutations of C/EBPα. The effects of FLT3-ITD cooperation with C/EBPα mutations in AML are not fully understood. To address this, knockin mouse strains harboring different Cebpa …
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Functions of Novel Ligand-independent Flt3 Alleles and RANKL in Promoting Dissemination of Murine B-Cell Leukemias to the Central Nervous System
… replaced N-terminal Fms-like tyrosine kinase 3 (Flt3) exons with endogenous retrovirus (ERV) transcriptional control elements. ERV-Flt3 fusion genes encoded truncated FLT3 (trFLT3) proteins that induced ligand-independent STAT5 phosphorylation and proliferation of hematopoietic progenitor cells. …
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Doxorubicin combined with phytochemicals as pro-apoptotic agents and protein kinase inhibitors for the treatment of acute myeloid leukaemia
… leukaemia with several kinase mutations. The FLT3-ITD mutation is a common kinase mutation observed in (20-30%) of AML patients and this mutation is also the most involved in the prognosis of AML. It confers poor treatment outcome in patients despite intensive chemotherapy due to an increased …
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Genetic Mechanisms of Transcriptional Regulation in Childhood Acute Lymphoblastic Leukemia
… fusion genes transcriptionally upregulate FLT3 expression as being a therapeutic target. Specific aims in this study include: 1) identifying the causal variant of ARID5B, 2) identifying molecular mechanism underlying drug resistance, 3) identifying molecular mechanism of transcriptional …
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Cytogenetically normal acute myeloid leukaemia at a single centre in South Africa
… tyrosine kinase internal tandem duplication (FLT3-ITD) and CCAAT/enhancer binding protein alpha (CEBPα) mutations in accordance with the ELN 2017 guidelines. Methods A review of cytogenetic results for all adult de novo AML cases diagnosed at Groote Schuur Hospital between 2005 and 2018 was …
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The development of a flow cytometric method to detect the presence of mutated nucleophosmin in Acute Myeloid Leukaemia
… if present alone (not associated with FLT3 internal tandem duplications (FLT3-ITD)) is associated with significantly better overall survival and disease free survival in AML and has been entered as a provisional category in the World Health Organisation (2008) classification of Acute …
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Characterisation of the effects and mechanism of action of rapamycin and genistein on acute myeloid leukemia using high-throughput techniques
… inhibited the constitutive phosphorylation of FLT3 in the MV4-11 cells, which carry the FLT3-ITD (Internal Tandem Duplication) mutations. However, GEN had potent anti-leukemic effects on the HL-60 cells too, in spite of them possessing the wild-type version of the gene. A purely proteomic-based …
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Development of novel receptor tyrosine kinase inhibitors by a chemocentric approach
… gave several potent compounds, inhibiting AXL, FLT3, and RET, with one compound being selective for AXL. The leads from this series were optimised further, through SAR studies, gaining important structural information in order to improve potency and selectivity of the compounds. The flexibility …
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Investigating the translational and metabolic reprogramming of the bone marrow niche in myeloid malignancy
… 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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Ribonuclease H2, RNA:DNA hybrids and innate immunity
… cytokine response exclusively in Flt3-L bone marrow cultures. This response was completely dependent on signalling involving MyD88 and/or Trif, however the specific receptor involved remains to be determined. Reduced cellular RNase H2 activity did not affect the ability of Flt3-L …
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Studies of immune biology of the common marmoset: a novel non-human primate transplant model.
… DC following treatment with the growth factor FLT3-Ligand. A three-colour flow cytometry strategy for identifying and sorting marmoset putative peripheral blood myeloid DC was validated. The rare myeloid DC population was expanded massively by FLT3-Ligand, and could be isolated in numbers …
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