Figure 1. Exposure to infection is a causal factor in B-precursor acute lymphoblastic leukemia as a result of Pax5 inherited susceptibility. (A) In humans, PAX5 c.547G>A predisposes to pB-ALL. Retention of PAX5 hypomorphic allele and deletion of the wild type PAX5 allele is observed in about 30% of PAX5 c.547G>A carriers and results in pB-ALL development. All leukemia show deletions of chromosome 9p. However, knowledge about preleukemic cell populations and environmental exposure is not yet available in carrier families. (B) Without somatic secondary genetic events – e.g. loss of the wt PAX5 allele - no pB-ALL develops (C) Pax5+/− mice acquire point mutations in the second allele of Pax5 when they are exposed to infection and this triggers pB-ALL development. (D) Pax5+/− mice do not develop leukemia under non-infection exposure conditions.
ß: point mutation; +: wild type Pax5 allele; -: deletion of Pax5 allele.