Submitted March 1, 2007
Accepted June 6, 2007
Screening for leukemia- and clone-specific markers at birth in children with T cell precursor ALL suggests a predominantly postnatal origin
Susanna Fischer, Georg Mann, Marianne Konrad, Markus Metzler, Georg Ebetsberger, Neil Jones, Bertrand Nadel, Olaf Bodamer, Oskar A Haas, Klaus Schmitt, and E Renate Panzer-Grumayer*
CCRI, Children's Cancer Research Insitute, St. Anna Kinderkrebsforschung, Vienna, Austria
St. Anna Kinderspital, Vienna, Austria
Department of Pediatrics, University of Erlangen, Erlangen, Germany
Department of Pediatrics, Landeskinderklinik Linz, Linz, Austria
Department of Pediatrics, University of Salzburg, Salzburg, Austria
Centre d'Immunologie de Marseille-Luminy, CNRS-INSERM-Universite de la Mediterranee, Marseille, France
Department of Pediatrics, Medical University of Vienna, Vienna, Austria
* Corresponding author; email: renate.panzer{at}ccri.at.
Childhood T cell precursor (TCP) ALL is an aggressive disease with a presumably short latency that differs in many biological respects from B cell precursor (BCP) ALL. We therefore addressed the issue of in utero origin of this particular type of leukemia by tracing oncogenic mutations and clone-specific molecular markers back to birth. These markers included various first and second hit genetic alterations (TCRD-LMO2 breakpoint regions, n=2; TAL1 deletions, n=3; Notch1 mutations, n=1), and non-oncogenic T cell receptor rearrangements (n=13) that were derived from leukemias of 16 children, who were 1,5 - 11,2 years old at diagnosis of leukemia. Despite highly sensitive PCR approaches (one cell with a specific marker among 100.000 normal cells), we identified the leukemic clone in the neonatal blood spots in only one young child. These data suggests that in contrast to BCP ALL the vast majority of TCP ALL cases are initiated after birth.
