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Blood, Vol. 96 No. 1 (July 1), 2000:
pp. 264-268
Detection of clonotypic IGH and TCR rearrangements in the neonatal
blood spots of infants and children with B-cell precursor acute
lymphoblastic leukemia
Tomohito Yagi,
Shigeyoshi Hibi,
Yasuhiro Tabata,
Kikuko Kuriyama,
Tomoko Teramura,
Tetsuo Hashida,
Yoshitaka Shimizu,
Tetsuya Takimoto,
Shinjiro Todo,
Tadashi Sawada, and
Shinsaku Imashuku
From the Department of Pediatrics, Kyoto Prefectural University of
Medicine, Kyoto, Japan; the Department of Pediatrics, Otsu Red Cross
Hospital, Otsu, Japan; and Kyoto City Institute of Health and
Environmental Sciences, Kyoto, Japan.
An attractive hypothesis is that in utero exposure of hematopoietic
cells to oncogenic agents can induce molecular changes leading to overt
acute lymphoblastic leukemia (ALL) in infants and perhaps older
children as well. Although supported by studies of identical infant
twins with concordant leukemia, and of nontwined patients with
MLL gene rearrangements, this concept has not
been extended to the larger population of B-lineage ALL patients
who lack unique nonconstitutive mutations or abnormally
rearranged genes. We therefore sought to demonstrate a prenatal origin
for 7 cases of B-cell precursor ALL (either CD10+ or
CD10 ) that had been diagnosed in infants and
children 14 days to 9 years of age. Using a polymerase chain
reaction-based assay, we identified the same clonotypic
immunoglobulin heavy-chain complementarity determining region or T-cell
receptor VD2-DD3 sequences in the neonatal
blood spots (Guthrie card) and leukemic cell DNAs of 2 infants with
CD10 ALL and 2 of the 5 older patients with
CD10+ ALL. Nucleotide sequencing showed a paucity of N or
P regions and shortened D germ line and conserved J sequences,
indicative of cells arising from fetal hematopoiesis. Our findings
strongly suggest a prenatal origin for some cases of B-cell
precursor ALL lacking specific clonotypic abnormalities.
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