1049-LSC Subtypes Driving Venetoclax Resistance in AML

Paper Talk · May 29, 2026 · 20m

This research identifies four distinct subtypes of leukemic stem cells (LSCs) in acute myeloid leukemia that dictate how patients respond to the drug venetoclax. By profiling over 150 patients, the authors discovered that resistance often stems from LSC plasticity, where cells shift into a megakaryocytic/erythroid state or exist as a rare LAMP5+ monocytic/dendritic (MoDe) subtype. These specific cellular states allow the cancer to bypass BCL-2 inhibition by relying on alternative survival proteins like MCL-1 or BCL-xL. Crucially, the study demonstrates that these resistant LSCs possess unique…