IL2R overexpression

This finding was reproduced in AML without a core-binding factor in the Children's Oncology Group study cohort. High CD25 expression has prognostic significance in pediatric AML.

Here we show the experimental development of a third-generation CAR-NK therapy strategy against the CD25 based on the scFV of the clinically approved monoclonal humanized antibody, Basiliximab... We show here for the first time the potential use of an NK cell-mediated CAR therapy strategy targeting CD25 which has been shown to be upregulated in CML blast crisis. The experimental data show a significantly increased and selective in vitro and in vivo cytotoxicity of CD25 CAR-NK92 cells against CD25-expressing leukemia cells as compared to WT-NK92 cells. These results suggest that targeting CD25 by a CD25 CAR based on Basilixiamb's scFV might be an interesting tool in BC-CML and in all acute leukemias overexpressing CD25.

Finally, the hypothesis of AML with BCR::ABL1 arising from driver mutations on a BCR::ABL1 background behaving as a clonal hematopoiesis mutation is discussed. Validation of our data in larger cohorts and basic research are needed to better understand the molecular and cellular aspects of AML with a BCR::ABL1 entity.

In summary, we have discovered a novel therapeutic anti-CD25 mAb that can deplete Treg cells without blocking IL-2 signaling. As demonstrated in our preclinical tumor models, it has a good potential to induce effective antitumor immune responses in TME and tumor growth inhibition especially in combination with PD-1/PD-L1 treatment.

iPSCs are a valuable tool to model CML progression and to identify new targets. Here, we show the relevance of CD25 identified in the iPSC model as a marker of CML progression.

Most cases of ALK+ ALCL highly express CD25 indicating that CD25 is a potential therapeutic target for ALCL patients. In this study, low CD25 expression identified a subset of ALK+ ALCL cases associated with older patient age, thrombocytopenia and shorter OS. These data suggest that assessing CD25 in ALK+ ALCL may be useful for guiding targeted therapy and in predicting prognosis of patients with ALK+ ALCL.

Overall, our results provide a novel iPSC-based experimental tool to study CML progression, allowing to reveal genetic abnormalities that correlate with those observed in primary BC. They also suggest that iPSC technology could pave the way for discovering new therapeutic targets, not only for CML progression, but also for several other hematological malignancies progressing towards aggressive phases.