Cobll1-flox Mouse

Cobll1, or cordon-bleu-like 1, is a gene that plays significant roles in multiple biological processes and diseases. It contains an actin-binding domain, and its functions are associated with cell morphology regulation, hematopoiesis, and various signaling pathways. For example, it is involved in pathways related to drug resistance and disease progression in leukemia [1,2].

In chronic myeloid leukemia (CML), Cobll1 affects blast crisis (BC) progression and tyrosine kinase inhibitor (TKI) resistance. It interacts with PACSIN2 and SH3BP1 to regulate TKI-mediated apoptosis. Cobll1 preferentially binds to PACSIN2, releasing SH3BP1 to promote the SH3BP1/Rac1 pathway, which suppresses TKI-mediated apoptosis and leads to TKI resistance. Also, Cobll1 increases IKKγ stability, activating NF-κB and reducing nilotinib-dependent apoptosis. High expression of Cobll1 confers drug resistance in CML cell lines and patient samples, and its expression is dramatically increased in BC compared to the chronic phase, correlating with a poor survival rate. Additionally, in zebrafish, the paralog Cobll1b is important for normal hematopoiesis during embryonic development [1,2].

In conclusion, Cobll1 is crucial in regulating cell behavior and disease progression, especially in CML where it is linked to drug resistance and blast crisis. The insights from studies on Cobll1, including those in zebrafish as a model, enhance our understanding of its biological functions and offer potential therapeutic targets for CML-BC.