Fig 4.
High-level BCL2 expression, but not BCL-w or BCL-xl, in peripheral blood chronic lymphocytic leukemia cells and inverse correlation of MCL1 expression with response. The concentrations of BCL2, BCL-w, BCL-xl, BIM, and MCL1 were measured as described in Patients and Methods by using immunoblots. BCL-xl was typically not detected (< 6 fmol/106 cells). (A) Concentrations of BCL2 and BCL-w for individual patients treated at two centers. (B and C) BCL2 concentrations and BIM:BCL2 ratios determined for 10 patients treated with ≥ 110 mg/d navitoclax v best observed clinical response (P = .3 and P = .06, respectively; unpaired two-tailed t test). (D) Shows significant inverse relationship between MCL1 expression in peripheral blood lymphocytes and the maximal reduction in peripheral blood lymphocytosis in the nine patients in whom it could be measured (Spearman coefficient r = −0.63; one-tailed P = .04), as hypothesized. (E and F) MCL1 concentrations and BIM:MCL1 ratios determined for the same patients v best observed clinical response (P = .1 and P =.03, respectively; unpaired two-tailed t test).