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 Blood, 15 October 2007, Vol. 110, No. 8, pp. 3036-3038.
Prepublished online as a Blood First Edition Paper on June 8, 2007; DOI 10.1182/blood-2007-03-077339.

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NEOPLASIA

Brief Report

Screening for leukemia- and clone-specific markers at birth in children with T-cell precursor ALL suggests a predominantly postnatal origin

Susanna Fischer1, Georg Mann2, Marianne Konrad1, Markus Metzler3, Georg Ebetsberger4, Neil Jones5, Bertrand Nadel6, Olaf Bodamer7, Oskar A. Haas2, Klaus Schmitt4, and E. Renate Panzer-Grümayer1,2

1 Children's Cancer Research Institute (CCRI), St Anna Kinderkrebsforschung, Vienna, Austria; 2 St Anna Kinderspital, Vienna, Austria; 3 Department of Pediatrics, University of Erlangen, Germany; 4 Department of Pediatrics, Landeskinderklinik Linz, Linz, Austria; 5 Department of Pediatrics, University of Salzburg, Salzburg, Austria; 6 Centre d'Immunologie de Marseille-Luminy, Institut National de la Santé et de la Recherche Médicale (INSERM)–Université de la Méditerranée, Marseille, France; and 7 Department of Pediatrics, Medical University of Vienna, Vienna, Austria

Childhood T-cell precursor acute lymphoblastic leukemia (TCP ALL) is an aggressive disease with a presumably short latency that differs in many biologic 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 nononcogenic T-cell receptor rearrangements (n = 13) that were derived from leukemias of 16 children who were 1.5 to 11.2 years old at diagnosis of leukemia. Despite highly sensitive polymerase chain reaction (PCR) approaches (1 cell with a specific marker among 100 000 normal cells), we identified the leukemic clone in the neonatal blood spots in only 1 young child. These data suggest that in contrast to BCP ALL most TCP ALL cases are initiated after birth.


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