16 research outputs found
Uncracked joints in plain concrete pavements: causes, effects and possibilities of improvements
On the diffusion of nautical knowledge from the Netherlands to north-eastern Europe, 1550-1850 '
Experimental and numerical investigation of wood fracture mechanisms at different humidity levels
Failure mechanisms in wood-based materials: A review of discrete, continuum, and hybrid finite-element representations
Modeling crack propagation in wood and wood composites. A review COST Action E35 2004–2008: Wood machining – micromechanics and fracture
Pseudo-beam method for compressive buckling characteristics analysis of space inflatable load-carrying structures
MCL-1 and PKA/AMPK Axis Fuel Venetoclax Resistance in Lymphoid Cancers
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3D FEM analysis of flexible base asphalt pavement structure under non-uniform tyre contact pressure
Mitochondrial Reprogramming Underlies Resistance to BCL-2 Inhibition in Lymphoid Malignancies.
Mitochondrial apoptosis can be effectively targeted in lymphoid malignancies with the FDA-approved B cell lymphoma 2 (BCL-2) inhibitor venetoclax, but resistance to this agent is emerging. We show that venetoclax resistance in chronic lymphocytic leukemia is associated with complex clonal shifts. To identify determinants of resistance, we conducted parallel genome-scale screens of the BCL-2-driven OCI-Ly1 lymphoma cell line after venetoclax exposure along with integrated expression profiling and functional characterization of drug-resistant and engineered cell lines. We identified regulators of lymphoid transcription and cellular energy metabolism as drivers of venetoclax resistance in addition to the known involvement by BCL-2 family members, which were confirmed in patient samples. Our data support the implementation of combinatorial therapy with metabolic modulators to address venetoclax resistance