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doi: 10.1161/01.atv.13.4.590

Hanthorn, J

EEG Neurosci

Bruton tyrosine kinase (BTK) and B-cell lymphoma-2 (BCL-2) inhibitors have been widely used to treat CLL, but CLL cells become resistant to these treatments over time

Mechanistically, this combination is also expected to reduce intracellular methionine availability by increasing anabolic demand (via GCN2 inhibition) while imposing oxidative and metabolic stress (via GCLC inhibition), creating a state of methionine limitation without the normal GCN2-mediated adaptive response