Recent studies of familial ALL have identified rare germline mutations in PAX5 and SH2B3 with high penetrance.21, 22 More strikingly, germline TP53 mutations were found in ∼50% of children with low-hypodiploid ALL, suggesting that this subtype of ALL may be a manifestation of Li Fraumeni syndrome.23 Together, these data raise the possibility that the proportion of ALL cases attributable to inherited genetic mutations may be much higher than currently proposed. Here, TP53 is linked to acute lymphoblastic leukemia.