Patient cell drug profiling identifies p53-linked vulnerabilities in refractory lymphoid malignancies

Relapsed/refractory lymphoid malignancies lack effective treatment selection strategies. We evaluated high-throughput ex vivo drug profiling in 26 patients, achieving successful profiling in 22 cases. We found broad ex vivo resistance to conventional chemotherapy but sensitivity to BH3 mimetics. Notably, p53-aberrant samples showed increased sensitivity to dasatinib and PI3K inhibitors across subtypes. These findings demonstrate feasibility of functional precision medicine pipelines in lymphoid malignancies and identify actionable vulnerabilities warranting further investigation.