These results demonstrate that Cobll1/SH3BP1‐dependent CML progression is independent of BCR‐ABL1 and that the Cobll1/PACSIN2/SH3BP1 regulatory cascade can be a novel target for drug resistance and disease progression in CML in a BCR‐ABL1‐independent manner. The gene discussed is PACSIN2; the disease is chronic myelogenous leukemia, BCR-ABL1 positive.