A review of: Wiemels JL, Cazzaniga G, Daniotti M, Eden OB, Addison GM, Masera G, Saha V, Biondi A, Greaves MF 1999 Prenatal origin of acute lymphoblastic leukaemia in children. Lancet 354:1499–1503

A most important observation has been reported recently by Wiemals et al., which has bearing on our understanding of leukemia and of the storage of autologous cord blood as “biological insurance.” Wiemels et al. report that the cord blood of children who subsequently developed acute lymphoblastic leukemia (ALL) contained leukemic cells.

They studied 12 children plus two identical twins who developed ALL between ages 2 to 5 years. The leukemic cells of all these children contained a fusion gene TEL-AML1, which was identified by PCR. TEL-AML 1 is the most common gene abnormality in ALL; it is found in the leukemic cells of approximately 25% of children with ALL. They examined archived neonatal blood spots that had been taken routinely to screen for phenylketonuria (PKU), etc. In six of nine which could be studied they found that the TEL-AML1 fusion gene could be identified. These observations mean that the blood of these newborn infants contained occult leukemic cells, which evolved into ALL years later.

A prenatal origin of ALL is not restricted to the TEL-AML1 type of leukemia. This is supported by the earlier report of leukemic cells in the blood of newborns who developed ALL associated with an MLL-AF4 fusion gene (1). ALL has a peak incidence in childhood of 2–5 years, which might result from expansion of a small clone at birth to overt disease several years later. It is also possible that prenatal events, such as the translocation leading to the formation of the TEL-AML1 fusion gene, are only the first step in leukemogenesis and that other genetic mutational “hits,” which result in acute leukemia, occur after birth. Presumably these studies will be expanded to definitively determine the frequency of leukemic cells in the cord blood of children who subsequently develop leukemia. Therefore any search for leukemogenic agents should distinguish those that affect the fetus from those that affect the child. These considerations must influence the planning and interpretation of any studies of environmental factors, such as ionizing radiation, electromagnetic fields, and viral infections.

There is considerable evidence to suggest that other childhood tumors arise in utero. The association between congenital anomalies and the occurrence of childhood cancer supports this concept (2).

The finding of leukemic/preleukemic cells in neonatal blood also should affect the autologous use of cord blood. There are many commercial cord blood banks that offer to store cord blood as “biologic insurance” to be available in case that child develops a disease that can be cured by bone marrow transplantation. A major potential use would be in ALL; however, the study of Wiemels et al. indicates that cord blood could not be used for this purpose. The same principle can be applied to the use of cord blood cells for autologous transplantation for solid tumors, a procedure with limited efficacy and which theoretically carries the potential of transplanting malignant cells. The only justification for autologous storage appears to be its potential use for family members. Inasmuch as the ideal cord blood transplant would be provided by an HLA matched donor, rather than a partially matched family donor, cells from large cooperative cord blood banks would be preferable. There appears to be little if any justification for the storage of cord blood cells for autologous use.