Presence of clone-specific antigen receptor gene rearrangements at birth indicates an in utero origin of diverse types of early childhood acute lymphoblastic leukemia

There is strong evidence that infant leukemias with a t(4;11) translocation originate in utero, To test whether other subtypes of childhood leukemias are also initiated during fetal life, we used clone-specific genetic marker s for the analysis of neonatal blood spots from 5 children aged 6 months to 4 years 8 months at diagnosis of pro-B, common acute lymphoblastic leukemi a (ALL), and T-ALL, In all children, the clonotypic antigen receptor gene r earrangements were already present at birth. The estimated amount of clonot ypic cells was in the range of 10 to 100 cells per blood spot, in 2 infants with a t(4;11) positive ALL, we detected similar amounts of the fusion gen e sequences compared with the clonal antigen receptor gene rearrangements, suggesting the presence of both markers in the same cells. Our data Indicat e that the first leukemogenic event of diverse types of childhood ALL may a lready occur in utero.(Blood. 2000;95:2722-2724) (C) 2000 by The American S ociety of Hematology.