A novel resistance mechanism was suggested, where the CELSR2 protein, as a mediator of a non-canonical Wnt signaling (204), positively controls the NR3C1 and negatively the BCL2. Based on these findings, a combined treatment with PRD and Bcl-2 antagonist venetoclax was proposed and successfully validated on CELSR2 knock-down leukemia cells and xenografted models. The gene discussed is CELSR2; the disease is leukemia.