Cathepsin G is associated with cerebral vascular injury in myeloid leukemia: a pathologic insight into intracranial hemorrhage.

BACKGROUND

Intracranial hemorrhage (ICH) is a fatal complication of leukemia; however, mechanisms underlying its development, particularly central nervous system (CNS) involvement and vascular injury, remain unclear.

OBJECTIVES

We aimed to investigate the histopathologic features of cerebral vessels in leukemia and the expression of hemostasis-related factors in leukemia cells.

METHODS

We conducted an autopsy-based study including 37 leukemia cases and 20 matched controls. Histopathologic analysis of CNS tissues was performed to evaluate ICH, leukemia cell localization, and vascular injury. Immunohistochemistry was performed to assess expression of vascular endothelial growth factor (VEGF), cathepsin G, tissue-type plasminogen activator, urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor, and tissue factor in leukemia cells. Vascular integrity was evaluated using stains for smooth muscle actin, collagen, fibrin, and von Willebrand factor.

RESULTS

ICH was identified in 68% of leukemia cases and was associated with fatal brain herniation in 40%. CNS involvement was observed in 54% 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-type 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.

CONCLUSION

VEGF and cathepsin G may serve as markers of meningeal invasion and cerebral vascular damage in leukemia, respectively.