Protracted postnatal natural histories in childhood leukemia

Studies of monozygotic twins with concordant leukemia and scrutiny of archived neonatal blood by polymerase chain reaction (PCR) indicated that many pediatric leukemias are initiated prenatally by chromosomal translocation followed by a variable postnatal period before diagnosis of disease. The latter is thought to reflect a persistent preleukemic stage and a requirement for secondary genetic events. We sought to examine this further by examination of blood spots in rare cases of MLL fusion-positive or ETV6/RUNX1 (TEL-AML1) fusion gene-positive acute leukemia that were diagnosed at ages beyond the normal age range. We present evidence that the duration of the postnatal preleukemic state can occasionally be very protracted in these biological subtypes of pediatric leukemia, and we discuss its biological significance.