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Showing 1 to 14 of 14 for “"MLL-AF9"”.
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Oncogenic roles of RAS in acute myeloid leukemia cooperated with Mll-AF9.
… which 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 …
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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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The Specific Role of the MLL CXXC Domain in MLL Fusion Protein Function
<p>The MLL gene was first identified because it is involved in chromosome translocations which produce novel fusion proteins that cause leukemia. The CXXC domain of MLL is a cysteine rich DNA binding domain with specificity for binding unmethylated CpG-containing DNA. The CXXC domain is retained in …
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Role of S6K1 in regulating self-renewal of hematopoietic stem cells and propagatoin of leukemia
… leukemia (AML). The mixed-lineage leukemia (MLL) gene is required for the maintenance of adult HSCs. Translocations in MLL are detected in approximately 5-10% of adult acute leukemia patients and in approximately 70% of acute leukemias in infants. We expressed MLL-AF9 fusion oncoprotein in …
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Critical Functions Specified by the MLL CXXC Domain Determine Leukemogenic Capacity
<p>TheMixed Lineage Leukemia(MLL) gene can participate in chromosomal translocations which generate a fusion protein leading to acute leukemia. A better understanding of how MLL fusion proteins contribute to leukemia is necessary in order to develop more effective treatments. In my dissertation …
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Significance of Protein Interactions in Mediating AF9 Function
<p>Rearrangements of the MLL gene at chromosome band 11q23 have been associated with a heterogeneous group of lymphoid, myeloid and mixed lineage leukemias. MLL rearrangements occur approximately in 70% of infant leukemias and are also common in therapy-related leukemias where patients were …
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Investigating the translational and metabolic reprogramming of the bone marrow niche in myeloid malignancy
… models 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
… by the translocation of Mixed-lineage leukemia (MLL) gene. Mice transplantation with KAT7 knock-out AML cell line showed delayed disease progression and prolonged survival compared to those injected with the wild-type counterpart. The acetyltransferase activity of KAT7 is essential for MLL-fusion …
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Cold Shock Domain Proteins in Normal and Leukemic Hematopoiesis
… of 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 …
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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 …
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Mechanistic Insights into Direct Interactions that Mediate the Activity of DOT1L Complex in MLL-Rearranged Leukemia
… of the N terminus of the Mixed Lineage Leukemia (MLL) protein to various partner proteins. Although more than 60 different translocation-based fusion proteins have been identified, fusion partners such as AF9, AF10, and ENL constitute the majority of the MLL-rearranged leukemia cases; …
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From Mechanisms of Leukaemogenic Dysregulation to New Candidate Therapeutics
… capabilities. Rearrangements involving the *MLL1* gene (*Kmt2a*) produce powerful oncogenic proteins occurring predominantly in paediatric and infant acute myeloid and lymphoid leukaemias. Despite having more than 80 fusion partners, MLL-AF9, MLL-AF4 and MLL-ENL make up more than 60% of cases …
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Trim24 In Normal & Malignant Hematopoiesis
… loss 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, …