Leukostasis, a life-threatening condition associated with leukemia, occurs when leukemia cells accumulate in and around the vasculature of organs such as the brain and lungs, leading to intracranial hemorrhage and respiratory failure. Recent evidence has shown that leukostasis is not simply due to the overcrowding of leukemia cells, as originally thought, but may results from specific mechanical interactions. The proposed research will investigate the nanomechanics of acute leukemia using atomic force microscopy (AFM) in an effort to improve the understanding and treatment of leukostasis. Quantitative mechanical properties of leukemia cells will be obtained by direct measurement of four poorly understood mechanisms likely involved in the condition: (1) deformability of individual leukemia cells, (2) cell-cell adhesion between leukemia cells leading to aggregation, (3) adhesion of leukemia cells to endothelium, and (4) transmigration of the leukemia cells into the endothelium. AFM data obtained with nanometer and nano-Newton resolution will provide new insight into the pathophysiology of leukostasis as well as guide targets for drug discovery and patient therapy.
NIH ExPorter
NIH ExPorter