Figure 4.

Effects of PROTAC YX-2-107 in Ph⁺ ALL cells and normal hematopoietic progenitors. Cell cycle analysis of BV173 cells (A) and SUP-B15 cells (B) after 48 hours of treatment with the indicated drug concentrations. Immunoblot of BV173 cells (C) and SUP-B15 cells (D) showing the expression of CDK6, CDK4, FOXM1, and phospho-RB after 72 hours of treatment with the indicated drug concentrations. Cell counts (Trypan blue staining) (mean ± standard deviation; 3 independent experiments) of palbociclib-treated and PROTAC YX-2-107–treated (1 µM added each day) BV173 (E) or SUP-B15 (F) cells. (G) Immunoblot for CDK4/CDK6 expression (left) and number of S-phase cells (represented as the percentage of drug-treated vs untreated cells taken as 100) (right) in YX-2-107–treated Ph⁺ ALL cells (sample #004). (H-J) Immunoblot for CDK4/CDK6 expression and percentage of S-phase cells in YX-2-107–treated normal hematopoietic progenitors and BV173 cells. (K) Cell cycle profile of CD34⁺ hematopoietic stem and progenitor cells (HSPC) transduced with anti-CDK4 or anti-CDK6 shRNA and selected with puromycin for 48 hours or treated with palbociclib (500 nM; 24 hours).