Leukemia‐derived exosomes and cytokines pave the way for entry into the brain

摘要: Infiltration of acute lymphoblastic leukemia (ALL) blasts into the CNS remains as a major clinical problem, with high risk for chemotherapy-resistant relapse and treatment-related morbidity. Despite common inclusion prophylaxis treatments in therapy regimens, there are significant gaps understanding mechanisms that mediate cell entry well roles resident cells brain. In this study, we employ xenograft model human B precursor (BCP)-ALL immunocompromised mice. This system recapitulates key pathological characteristics leptomeningeal involvement seen patients provides insights rare cases involve parenchymal invasion. We examine infiltration engrafted brains recipient mice provide evidence interaction between brain causes aberrant activation host microenvironment. BCP-ALL also release multiple cytokines exosomes containing IL-15 bind internalized by astrocytes vessel endothelial cells. Leukemic invasion is linked to production VEGF-AA disruption blood-brain-barrier (BBB) integrity. Knockdown either or IL-15Rα NALM6 line decreases These results important which lymphoblasts modulate microenvironment breach BBB metastatic