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Targeting BCL2 with venetoclax for DH-DPL
A
B
sion lymphoma cells.
Figure 6. Treatment with veneto- clax augments the binding of PP2A B56a to BCL2 in the dou- ble-hit and double-protein-expres-
(A) Immunoprecipitation (IP) and western blot (WB) analyses showed that BCL2 was bound to BIM and PP2A B56α at steady state. Rabbit (R) IgG was used as a negative control for the IP stud- ies. (B) Although total BIM pro- teins bound to BCL2 were decreased similarly in Karpas231 and OCI-Ly8 cells within 60 min after exposure to venetoclax dis- solved in dimethyl sulfoxide (DMSO), the proportion of B56α bound to BCL2 was slightly increased. Total BCL2 proteins
bound to BIM were decreased in the early phase of venetoclax treatment in both dou- ble-hit and double-protein-expres- sion lymphoma cell lines.
also
AB
Figure 7. A low concentration of venetoclax induces apoptosis in primary double-hit and double-protein-expression lymphoma cells. (A) The bone marrow examina- tion of one patient (UPN3) revealed massive infiltration by blastoid double-hit and double-protein-expression lymphoma (DH-DPL) cells with a mature B-cell phenotype terminal deoxynucleotidyl transferase (TdT)-negative and BCL6-positive [Wright-Giemsa (WG) stain x1000, hematoxylin-eosin (HE) stain x600]. Immunohistochemistry confirmed that the cells expressed high levels of MYC, BCL2, MCL1 and BIM (x600). (B) Flow cytometry clearly detected apoptotic changes 24 h after exposure to venetoclax dissolved in dimethyl sulfoxide (DMSO). More than 99% of blastoid DH-DPL cells were positive for annexin V.
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