title: Screening for leukemia- and clone-specific markers at birth in children with T-cell precursor ALL suggests a predominantly postnatal origin.
abstract: 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.
authors.affiliation: Children's Cancer Research Institute, St Anna Kinderkrebsforschung, Vienna, Austria.
authors.forename: Susanna
authors.initials: S
authors.lastname: Fischer
authors.forename: Georg
authors.initials: G
authors.lastname: Mann
authors.forename: Marianne
authors.initials: M
authors.lastname: Konrad
authors.forename: Markus
authors.initials: M
authors.lastname: Metzler
authors.forename: Georg
authors.initials: G
authors.lastname: Ebetsberger
authors.forename: Neil
authors.initials: N
authors.lastname: Jones
authors.forename: Bertrand
authors.initials: B
authors.lastname: Nadel
authors.forename: Olaf
authors.initials: O
authors.lastname: Bodamer
authors.forename: Oskar A
authors.initials: OA
authors.lastname: Haas
authors.forename: Klaus
authors.initials: K
authors.lastname: Schmitt
authors.forename: E Renate
authors.initials: ER
authors.lastname: Panzer-Grümayer
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002999:Clone Cells; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte / Q000235:genetics*; D006801:Humans; D007223:Infant; D060588:LIM Domain Proteins; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D008297:Male; D008667:Metalloproteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051881:Receptor, Notch1 / Q000235:genetics; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; D008667:Metalloproteins; D011518:Proto-Oncogene Proteins; D051881:Receptor, Notch1; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; C085117:LMO2 protein, human; C067143:TAL1 protein, human