Cell deformability enhances adhesion of ATRA-differentiated HL-60 cells to P-selectin.

Acute promyelocytic leukemia (APL) is characterized by immature myeloid cells with unlimited proliferative capacity. All-trans retinoic acid (ATRA) can induce these cells to differentiate, but patients may develop differentiation syndrome (DS), a life-threatening complication linked to abnormal leukocyte recruitment. The mechanisms of DS remain poorly understood, despite insights gained from studies on APL cell lines. In this study, ATRA-differentiated HL-60 cells were perfused into a flow chamber simulating the physiological environment and functionalized with P-selectin to mimic the initial step of leukocyte recruitment. We quantified the adhesive behavior of these cells by measuring the PSGL-1-P-selectin bond lifetime and adhesion rate with and without ATRA treatment. Both parameters increased following ATRA treatment. Flow cytometry revealed that the difference in PSGL-1 expression was minimal. To explore the impact of cell stiffness on adhesion, we fixed cells and performed additional flow chamber experiments. The bond lifetime and adhesion rate of differentiated cells decreased after fixation, suggesting that the altered adhesion behavior was mainly due to changes in cell deformability, with a minimal role played by PSGL-1 expression. These findings highlight the potential role of cell deformability in the enhanced adhesion of ATRA-differentiated cells, offering new insights into the mechanisms of DS and paving the way for improved prevention and treatment strategies for DS in APL patients.