B-ALL primarily affects pediatric patients. Zanetti et al demonstrate that CXCL13 produced by bone marrow macrophages in young mice activates CXCR5 in B-ALL cells, leading to fast leukemia growth and poor survival. Physiological aging results in the loss of the CXCL13-CXCR5 axis, leading to slower leukemia growth and improved survival. Their study demonstrates that the age of the microenvironment controls leukemia outcomes.