Leukemia is a commonly seen disease caused by abnormal differentiation of hematopoietic stem cells and blasting in bone marrow. Despite drugs are used to treat the disease clinically, the influence of these drugs on leukemia cells' biomechanical properties, which are closely related to complications like leukostasis or infiltration, is still unclear. Due to non-adherent and viscoelastic nature of leukemia cells, accurate measurement of their elastic modulus is still a challenging issue. In this study, we adopted rate jump method together with optical tweezers indentation to accurately measure elastic modulus of leukemia cells K562 after phorbol 12-myristate 13-acetate (PMA), all-trans retinoic acid (ATRA), Cytoxan (CTX), and Dexamethasone (DEX) treatment, respectively. We found that compared to control sample, K562 cells treated by PMA showed nearly a threefold increase in elastic modulus. Transwell experiment results suggested that the K562 cells treated with PMA have the lowest migration capability. Besides, it was shown that the cytoskeleton protein gene alpha-tubulin and vimentin have a significant increase in expression after PMA treatment by OCR. The results indicate that PMA has a significant influence on protein expression, stiffness, and migration ability of the leukemia cell K562, and may also play an important role in the leukostasis in leukemia. (C) 2019 Elsevier Inc. All rights reserved.