Acute lymphoblastic leukemia (ALL) has a marked propensity to metastasize to the CNS. In contrast to brain metastases from solid tumours, metastases of ALL seldom involve the parenchyma but are isolated to the leptomeninges, which is an infrequent site for carcinomatous invasion. Although metastasis to the CNS occurs across all subtypes of Acute lymphoblastic leukemia, a unifying mechanism for invasion has not yet been determined. The basement membrane of these bridging vessels is enriched in laminin. The laminin receptor α6 integrin is expressed in most cases of ALL. Mice with Acute lymphoblastic leukemia xenografts were treated with either a PI3Kδ inhibitor, which decreased α6 integrin expression on ALL cells. Our data suggest that α6 integrin expression, which is common in ALL, allows cells to use neural migratory pathways to invade the CNS.