MCL1 inhibitor induces apoptosis in Anaplastic Large Cell Lymphoma and in Primary Effusion Lymphoma

ABSTRACT: Overexpression of antiapoptotic BCL2 family proteins occurs in various hematologic malignanices and contributes to leukemogenesis by inhibiting the apoptotic machinery of the cells. BH3 mimetics provide an option for medication, with venetoclax as the first drug applied for chronic lymphocytic leukemia and for acute myeloid leukemia. To find additional hematologic entities with ectopic expression of BCL2 family members, we performed expression screening applying the LL-100 panel. Primary effusion lymphoma (PEL) and anaplastic large cell lymphoma (ALCL), 2/22 entities covered by this panel, stood out by high expression of MCL1 and low expression of BCL2. The MCL1 inhibitor AZD-5991 induced apoptosis in both malignancies suggesting that this BH3 mimetic might be efficient as drug for these diseases. The ALCL cell lines also expressed BCLXL and BCL2A1, both contributing to survival of the cells. The combination of specific BH3 mimetics yielded synergistic effects, pointing to a novel strategy for the treatment of ALCL. The PI3K/AKT inhibitor BEZ-235 could also efficiently be applied in combination with AZD-5991, providing an alternative to avoid thrombocytothemia, which is associated with the use of BCLXL inhibitors.

INSTRUMENT(S): GeneChip® Pico Kit (Affymetrix), Affymetrix Clariom™ S (400 Format), Affymetrix GCS 3000

ORGANISM(S): Homo sapiens

SUBMITTER: Claudia Pommerenke 

PROVIDER: E-MTAB-10903 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress