In our analysis, pretreatment with 2 known CypD inhibitors (NIM811 and CspA) effectively blocked the induction of apoptosis as well as the release of calcein AM from the mitochondria in DT-061–treated CLL cells (Figure 5 and Supplemental Figure 7), suggesting that PP2A activation overcame multidrug resistance through mPTP induction–dependent apoptosis. Here, PTPA is linked to B-cell chronic lymphocytic leukemia.