Antibiotic treatment in the development of lymphoblastic leukemia. Antibiotic treatment in early life induces leukemia in genetically predisposed Pax5^+/− mice.⁸¹ (Left) In wild-type mice, depletion of the gut microbiome bacteria by antibiotic treatment at 8 weeks of age has only a transient effect on the immune system (including the gut-associated and peripheral lymphoid tissues) and mice do not develop pB-ALL. (Right) Pax5 heterozygosity directly affects B-cell maturation and leads to clonal hematopoiesis, while also indirectly reducing gut microbiota diversity. In response to bacterial depletion in the gut microbiome by antibiotic treatment at 8 weeks of age, the microbiome reconstitutes with further reduced diversity. Cooperating oncogenic mutations then lead to pB-ALL in ∼50% of these mice between 11 and 21 months of age. Leukemia development is preceded by a reduction of mature B and T cells in the gut and associated peripheral lymphoid tissues. However, it has not been tested in this model whether leukemia development can be inhibited through intervention. In addition to microbial dysbiosis, infectious stimuli can also cooperate with oncogenic mutations, leading to leukemia development in Pax5^+/− mice.³¹