Acute Leukaemia Associated Hybrid Gene TEL/AML1 is Generated During Normal Foetal Developmentand Can Be Detected in Cord Blood of Healthy Newborns

Overview

Pre-natal origin of acute lymphoblastic leukaemia in children has been recently confirmed. The evidencecomprises the clonality studies of concordant leukaemias in monozygotic twins and several cases of backtrackingof leukaemic cell markers back to the material from the peri-natal period of life. These findings confirm that moreevents are necessary for the origin of acute leukaemia and lay the first event into the period of pre-natal life at leastin some types of leukaemia. This study concentrated on the detection ofmRNA of the TEL/AML1 hybrid gene thatis found in almost one quarter of all patients with acute lymphoblastic leukaemia. The origin of TEL/AML1 wasrecently attributed to the first leukaemogenic event. Authors analysed a total of 298 cord blood samples fromhealthy newborns and in 8 cases they identified TEL/AML1 positivity using (quantitative) reverse-transcriptasepolymerase chain reaction. Authors found positivity also in one of 12 foetal haematopoietic tissues tested. In onecase, they confirmed TEL/AML1positivity by fluorescent in situ hybridisation. In vitro experiments using cell linesand healthy donors cells did not confirm the hypothesis that TEL/AML1 fusion can originate due to apoptogenicstimuli during the period between the samples were taken and processed. These results demonstrate thatTEL/AML1-positive cells can be detected at birth and that the frequency of this finding is forty times higher thantotal cumulative probability for these children to develop TEL/AML1-positive leukaemia.

Key words:
paediatric acute lymphoblastic leukaemia, cord blood, TEL/AML1