SH2B3 and acute lymphoblastic leukemia: 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.