Mixed-lineage leukemia cells undergo unique adaptations in the CNS niche

Transcriptomic profiling of matched CNS- and BM-derived LPCs revealed enrichment of pathways involved in hypoxia, lipid and cholesterol homeostasis, and inflammatory signalling. Notably, LPC subsets that successfully adapted to the CNS niche upregulated lipid and fatty acid metabolic programmes. CNS-derived LPCs showed increased expression of genes involved in T cell immune modulation, suggesting a skew to a more immunosuppressive environment.

These findings indicate that the CNS niche imposes lasting metabolic, functional, and immunological constraints on leukemic cells, impairing their ability to reestablish systemic disease. We show that the CNS niche imposes selective pressures and causes functional reprogramming of mixed lineage LPCs, affecting their systemic repopulation capacity and, we hypothesise, immune cell interactions. We further believe this study has relevance to primary mixed lineage infant leukaemia and, increasingly important, lineage-switched infant leukaemia.