Cathepsin G is associated with cerebral vascular injury in leukemia: A pathological insight into intracranial hemorrhage

Intracranial hemorrhage (ICH) is a fatal complication of leukemia; however, the mechanisms underlying its development, particularly central nervous system (CNS) involvement and vascular injury, remain unclear. This autopsy-based study investigated the histopathological features of cerebral vessels in leukemia and the expression of hemostasis-related factors in leukemia cells. Thirty-eight leukemia cases and 20 matched controls were included. A histopathological analysis of CNS tissues was performed to evaluate ICH, leukemia cell localization, and vascular injury. Immunohistochemistry was conducted to assess the expression of vascular endothelial growth factor (VEGF), cathepsin G, tissue-plasminogen activator, urokinase-plasminogen activator, urokinase plasminogen activator receptor, and tissue factor in leukemia cells. Vascular integrity and permeability were evaluated using stains for smooth muscle actin, collagen, fibrin, and von Willebrand factor. ICH was identified in 66% of leukemia cases and was associated with fatal brain herniation in 40%. CNS involvement was observed in 59% of cases, often without a clinical diagnosis. The leukemia cell infiltration of meninges and vascular walls was frequently associated with changes in smooth muscle cells and adventitial collagen. CNS vascular injury was frequently associated with ICH in the presence of leukemia cell infiltration. VEGF and urokinase-plasminogen activator were highly expressed in leukemia cells. VEGF was associated with meningeal invasion, while cathepsin G was predominantly expressed in myeloid leukemia and linked to vascular damage. These results suggest that the leukemia cell infiltration of cerebral vascular walls plays an important role in cerebral vessel injury and leukemia cell-related ICH via VEGF and cathepsin G expression. Key pointsO_LILeukemia cell infiltration into cerebral vascular walls is associated with vascular damage and intracranial hemorrhage in autopsy cases. C_LIO_LIThe expression of VEGF and cathepsin G in leukemia may serve as markers of CNS involvement and cerebral vascular injury, respectively. C_LI