While CD20-targeted immunotherapies offer clinical benefit, their efficacy in BCP-ALL is limited by low and heterogeneous CD20 expression on leukemic cells. The authors show that overexpression of wild-type IKZF1, a tumor suppressor frequently mutated in high-risk BCP-ALL, upregulates CD20 and promotes leukemic B-cell maturation. Using bioinformatic tools, the team identified mTORC1 inhibitors as compounds mimicking the IKZF1-induced transcriptional signature. mTORC1 inhibition increased CD20 expression (in vitro and in vivo) and enhanced the antitumor efficacy of anti-CD20 monoclonal antibodies. These findings provide a strong rationale for the clinical evaluation of mTORC1 inhibitors as adjuncts to anti-CD20 immunotherapy in BCP-ALL.
The study includes contributions from our department PhD student Zuzanna Nowicka and department head Prof. Wojciech Fendler. Congratulations to the whole team!