An Analysis Of Mechanisms Of Central Nervous System Infiltration In Acute Lymphoblastic Leukaemia Using Primary Cells Xenografted Into Immunodeficient Mice

Despite great advances in the treatment of paediatric acute lymphoblastic leukaemia (ALL), disease in the central nervous system (CNS) continues to pose challenges. Current diagnostic tests are insensitive and risk factors for CNS relapse are poorly understood. This results in all children receiving intensive CNS-directed therapy which may be associated with acute and/or chronic neurotoxicity. A better understanding of the mechanisms of CNS engraftment is a necessary pre-requisite for diagnostic and therapeutic advances. To investigate if primary cells infiltrate the CNS, and whether this property resides in any particular sub-clonal compartment we undertook a comprehensive analysis of the CNS engrafting potential of primary ALL cells in immunodeficient NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice. In addition, we used this model to investigate whether chemokine receptor expression drives CNS infiltration in pre-B ALL, as previously shown for T-ALL.