Acute leukaemia associated hybrid gene TEL/AML1 is generated during normal foetal development and can be detected in cord blood of healthy newborns
Abstract
Pre-natal origin of acute lymphoblastic leukaemia in children has been recently confirmed. The evidence comprises the clonality studies of concordant leukaemias in monozygotic twins and several cases of backtracking of leukaemic cell markers back to the material from the peri-natal period of life.
These findings confirm that more events are necessary for the origin of acute leukaemia and lay the first event into the period of pre-natal life at least in some types of leukaemia. This study concentrated on the detection of mRNA of the TEL/AML1 hybrid gene that is found in almost one quarter of all patients with acute lymphoblastic leukaemia.
The origin of TEL/AML1 was recently attributed to the first leukaemogenic event. Authors analysed a total of 298 cord blood samples from healthy newborns and in 8 cases they identified TEL/ AML1 positivity using (quantitative) reverse-transcriptase polymerase chain reaction.
Authors found positivity also in one of 12 foetal haematopoietic tissues tested. In one case, they confirmed TEL/AML1 positivity by fluorescent in situ hybridisation.
In vitro experiments using cell lines and healthy donors cells did not confirm the hypothesis that TEL/AML1 fusion can originate due to apoptogenic stimuli during the period between the samples were taken and processed. These results demonstrate that TEL/AML1-positive cells can be detected at birth and that the frequency of this finding is forty times higher than total cumulative probability for these children to develop TEL/AML1-positive leukaemia.