Childhood leukaemia and various subtypes

Although there are no accurate data for concordance rates of leukaemia in infant twins, it seems to be very high, and perhaps approaching one hundred percents. If this is correct, it suggests that MLL gene fusion in utero has a dramatic impact, ensuring subsequent leukaemia. But for children aged between two and six years who have acute lymphoblastic leukaemia, the concordance rate is considerably lower at around five percents.

This still represents a one hundred fold extra risk of leukaemia for the twin of a patient with acute lymphoblastic leukaemia but also indicates the need for some additional postnatal events for which there is a one in twenty chance, or ninety five percent discordance. This actually suggests, at a minimum, a two hit model for the natural course of childhood leukaemia.

If this model of leukaemia development is correct, then for every child with acute lymphoblastic leukaemia diagnosed, there should be at least twenty healthy children who actually have had a chromosome translocation, a functional leukaemia fusion gene, and a covert pre leukemic clone generated in utero.
This possibility has been investigated by screening unselected samples of newborn cord blood for fusion genes. Cord blood is actually the best place to find stem cells especially if you want to do umbilical cord blood collection and then go to a cord blood bank or stem cell bank to store it just in case.

The real bottleneck in development of acute lymphoblastic leukaemia therefore seems to be a stringent requirement for a second hit after birth, which is exposure and additional chromosomal or molecular abnormality.

A key issue to resolve is what exposures or events might precipitate the chromosome breaks whose improper repair initiates or promotes childhood leukaemia. Given the biological diversity of leukaemia, it is highly unlikely that there is a single cause. Even for a defined biological subtype of the disease, there probably is not one cause as such but a causal mechanism. As with other cancers, this is likely to involve an interaction of exposure with inherent genetic susceptibility, and chance.
Epidemiological evidence suggests that ionising radiation, certain chemicals, viruses and bacteria may actually play a part in the development of some subtypes of leukaemia and lymphoma in adults and children. Whether any of these exposures have a major role in childhood leukaemia is uncertain, but large scale case control molecular epidemiological studies in Great Britain and the United States if America may provide answers. Doing stem cell storage or cord blood storage in a cord blood bank or a stem cell bank could be a good solution as breakthrough seems to happen more and more often.