BCL-xL expression increases as patients with MPN progress to post-MPN AML. Targeting of BCL-xL and BCL-2 through ABT-263 leads to dose-limiting thrombocytopenia because of the fact that platelets depend on BCL-xL for survival. However, degradation of BCL-xL, mediated by PROTAC DTT2216, only targets VHL-expressing cells, which is not expressed in platelets, thereby killing leukemic cells while minimizing on-target platelet toxicity.