Presence of clone-specific markers at birth in children with acute lymphoblastic leukaemia.
Recent studies have suggested that development of childhood acute lymphoblastic leukaemia may often be initiated in utero. To provide further evidence of an prenatal origin of childhood leukaemia, we conducted a molecular biological investigation of nine children with B-precursor acute lymphoblastic leukaemia carrying the chromosomal translocation t(12;21), the most common subtype of all childhood acute lymphoblastic leukaemia. Specifically, for each child we identified the non-constitutive chromosomal sequences made up by the t(12;21) fusion gene. From these, leukaemia clone-specific DNA primers were constructed and applied in nested polymerase chain reaction analyses of DNA extracted from the patients' Guthrie cards obtained at birth. Leukaemia clone-specific fusion gene regions were demonstrated in Guthrie card DNA of three patients, age 2 years 11 months, 3 years 4 months, and 5 years 8 months at leukaemia diagnosis. Our findings are consistent with previous observations, and thus provide further evidence that the development of t(12;21) B-precursor acute lymphoblastic leukaemia may be initiated in utero. Review of the current literature moreover indicates that age at leukaemia may be inversely correlated with the burden of cells with leukaemia clonal markers, i.e. leukaemia predisposed cells at birth, and that certain types of childhood acute lymphoblastic leukaemia develop as a multiple step process involving both pre- and postnatal genetic events.
Hjalgrim
L L
LL
Department of Epidemiology Research, Danish Epidemiology Science Centre, Statens Serum Institut, Artillerivej 5, DK- 2300 Copenhagen S, Denmark.
Madsen
H O
HO
Melbye
M
M
Jørgensen
P
P
Christiansen
M
M
Andersen
M T
MT
Pallisgaard
N
N
Hokland
P
P
Clausen
N
N
Ryder
L P
LP
Schmiegelow
K
K
Hjalgrim
H
H
D000293:Adolescent; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics*; D001800:Blood Specimen Collection; D002648:Child; D002675:Child, Preschool; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D050676:Core Binding Factor Alpha 2 Subunit; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D016133:Polymerase Chain Reaction; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics; D000097764:ETS Translocation Variant 6 Protein
D014408:Biomarkers, Tumor; D050676:Core Binding Factor Alpha 2 Subunit; D017931:DNA Primers; D004273:DNA, Neoplasm; D037601:Mannose-Binding Lectin; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein