AACR 2017 | Poster 2770/2 – BCL-2 overexpression is a predictive biomarker for the combination of ABT-199 with chemotherapy in Diffuse Large B-Cell Lymphoma cell lines

On Monday 3^rd April during this year's American Association for Cancer Research (AACR) annual meeting, a poster (2770 / 2) by Ian McConnell, from VCU Massey Cancer Center, Richmond, VA, et al. titled “Bcl-2 overexpression is a predictive biomarker for the combination of ABT-199 with chemotherapy in diffuse large B-cell lymphoma cell lines” was presented.

The group hypothesized that BCL-2 overexpression correlates with sensitivity to ABT-199 plus chemotherapy in DLBCL. To test this, they analyzed the effect of ABT-199 in four different DLBCL cell lines with different levels of BCL-2 expression: (from highest to lowest) CARNAVAL, OCI-ly18, SU-DHL-4, and SU-DHL-8.

Key Highlights:

• CARNAVAL was the most sensitive (IC₅₀ = ~7nM); SU-DHL-8 was the least sensitive (IC₅₀ = 10µM)
• The remaining 2 cell lines displayed intermediate sensitivity (45.9nM for OCI-ly18 and 2.6µM for SU-DHL-4)
• In CARNAVAL cells, the combination of either etoposide or doxorubicin chemotherapy with ABT-199 led to a significant reduction in cell viability at 48hrs versus each single agent alone
  • This was associated with induction of apoptosis measured by Annexin-V/PI, caspase-3, and PARP cleavage, an increase in γ-H2AX, and decrease in Mcl-1
• ABT-199 did not enhance the activity of chemotherapy in SU-DHL-8 cells

The poster was concluded by stating that these preclinical results support the use of BCL-2 overexpression as a predictive biomarker, enabling more accurate selection of DLBCL patients who are likely to benefit from combining ABT-199 with chemotherapy.