Collectively, our data showed for the first time that RanBP3 was a potential target for CML, and played a crucial role in regulating proliferation, apoptosis, and the IM chemosensitivity of CML cells by mediating the nuclear export of SMAD2/3 and ERK1/2, suggesting that targeting RanBP3 alone or combined with IM can improve the clinical response of refractory and resistant CML patients. Here, MAPK3 is linked to chronic myelogenous leukemia, BCR-ABL1 positive.