Screening for leukemia- and clone-specific markers at birth in children with T-cell precursor ALL suggests a predominantly postnatal origin.
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.
Fischer
Susanna
S
Children's Cancer Research Institute, St Anna Kinderkrebsforschung, Vienna, Austria.
Mann
Georg
G
Konrad
Marianne
M
Metzler
Markus
M
Ebetsberger
Georg
G
Jones
Neil
N
Nadel
Bertrand
B
Bodamer
Olaf
O
Haas
Oskar A
OA
Schmitt
Klaus
K
Panzer-Grümayer
E Renate
ER
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
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