Central nervous system involvement in childhood acute lymphoblastic leukemia is linked to upregulation of cholesterol biosynthetic pathways
Antony Cousins, O. Porta Olivares, Elke Markert, Anand Manoharan, X. Bubnova, Silvia Bresolin, M. Degn, Zhaoyan Li, D. Silvestri, G. McGregor, Sergey Tumanov, David Sumpton, Jurre J. Kamphorst, Alison M. Michie, Pawel Herzyk, M. G. Valsecchi, Allen Eng Juh Yeoh, Kjeld Schmiegelow, Geertruy te Kronnie, Eyal Gottlieb, Christina Halsey
Abstract
Treatment for childhood acute lymphoblastic leukemia (ALL) requires intensive intrathecal and systemic therapy to reduce the risk of central nervous system (CNS) relapse. This treatment is associated with high rates of neurotoxicity as well as being onerous for both patients and healthcare systems [ 1 ]. Improving CNS-directed therapy, requires understanding of the mechanisms of leukemic survival in this microenvironment, accompanied by better prognostic and predictive biomarkers for CNS leukemia. The former will underpin discovery of treatments with reduced toxicity, the latter is essential for the development of risk-adapted CNS-directed therapy.