The antitumor compound triazoloacridinone C-1305 inhibits FLT3 kinase activity and potentiates apoptosis in mutant FLT3-ITD leukemia cells
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منابع مشابه
Fluvastatin inhibits FLT3 glycosylation in human and murine cells and prolongs survival of mice with FLT3/ITD leukemia.
FLT3 is frequently mutated in acute myeloid leukemia (AML), but resistance has limited the benefit of tyrosine kinase inhibitors (TKI). We demonstrate that statins can impair FLT3 glycosylation, thus leading to loss of surface expression and induction of cell death, as well as mitigation of TKI resistance. Immunofluorescence microscopy confirms a reduction in surface localization and an increas...
متن کاملPim kinases modulate resistance to FLT3 tyrosine kinase inhibitors in FLT3-ITD acute myeloid leukemia
Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) is frequently detected in acute myeloid leukemia (AML) patients and is associated with a dismal long-term prognosis. FLT3 tyrosine kinase inhibitors provide short-term disease control, but relapse invariably occurs within months. Pim protein kinases are oncogenic FLT3-ITD targets expressed in AML cells. We show that increased Pim...
متن کاملTreatment of FLT3-ITD acute myeloid leukemia.
Acute myeloid leukemia (AML) is an aggressive hematologic malignancy which is cured in a minority of patients. A FLT3-internal tandem duplication (ITD) mutation, found in approximately a quarter of patients with de novo AML, imparts a particularly poor prognosis. Patients with FLT3-ITD AML often present with more aggressive disease and have a significantly higher propensity for relapse after re...
متن کاملFrequency of FLT3 ITD and FLT3 TKD Mutations in Multiple Myeloma Patients (A Case Control Study)
Background and Aims: Multiple myeloma is a malignant proliferation of plasma cells derived from a single clone. The tumor, its products and the host response lead to organ damages. Some factors that are responsible in its pathogenesis are recognized. As FMS like Tyrosine Kinase 3 receptor (FLT3) mutation has been proved as a determining factor in leukemic patients the goal of this study was to ...
متن کاملAzacitidine combined with the selective FLT3 kinase inhibitor crenolanib disrupts stromal protection and inhibits expansion of residual leukemia-initiating cells in FLT3-ITD AML with concurrent epigenetic mutations
Effectively targeting leukemia-initiating cells (LIC) in FLT3-ITD-mutated acute myeloid leukemia (AML) is crucial for cure. Tyrosine kinase inhibitors (TKI) have limited impact as single agents, failing to eradicate LIC in the bone marrow. Using primary AML samples and a patient-derived xenograft model, we investigated whether combining the FLT3-selective TKI crenolanib with the hypomethylating...
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ژورنال
عنوان ژورنال: Acta Pharmacologica Sinica
سال: 2015
ISSN: 1671-4083,1745-7254
DOI: 10.1038/aps.2014.142