Background. There is little current insight into the natural history of childhood leukaemia or the timing of relevant mutational events. TEL-AML1 gene fusion due to chromosomal translocation is frequently seen in the common form of childhood acute lymphoblastic leukaemia. We investigated whether this abnormality arises prenatally. Methods. We identified, by reverse-transcriptase PCR screening of blood or bone marrow, TEL-AML1 fusion in 12 children, plus a pair of identical twins, aged 2-5 years from Italy and the UK, who had newly diagnosed acute lymphoblastic leukaemia. We amplified and sequenced the genomic TEL-AML1 fusion gene with a long-distance inverse PCR method. Primers were designed that could be used in short-range PCR to screen for patient-specific, leukaemia clone-specific TEL-AML1 genomic fusion sequences in neonatal blood spots from each child. Findings. We initially identified TEL-AML1 fusion sequences in blood spots from the identical twins, diagnosed with concordant acute lymphoblastic leukaemia at age 4 years, who shared a single or clonotypic TEL-AML1 sequence that suggested prenatal origin in one twin. Three children were excluded because control genes could not be amplified. Of the other nine patients, six had positive blood spots. Blood spots that were classified as negative were uninformative. Interpretation. Our findings showed that childhood acute lymphoblastic leukaemia is frequently initiated by a chromosome translocation event in utero. Studies in identical twins show however that such an event is insufficient for clinical leukaemia and that a postnatal promotional event is also required.

Wiemels, J., Cazzaniga, G., Daniotti, M., Eden, O., Addison, G., Masera, G., et al. (1999). Prenatal origin of acute lymphoblastic leukaemia in children. THE LANCET, 354(9189), 1499-1503 [10.1016/S0140-6736(99)09403-9].

Prenatal origin of acute lymphoblastic leukaemia in children

Cazzaniga G.;Masera G.;Biondi A.;
1999

Abstract

Background. There is little current insight into the natural history of childhood leukaemia or the timing of relevant mutational events. TEL-AML1 gene fusion due to chromosomal translocation is frequently seen in the common form of childhood acute lymphoblastic leukaemia. We investigated whether this abnormality arises prenatally. Methods. We identified, by reverse-transcriptase PCR screening of blood or bone marrow, TEL-AML1 fusion in 12 children, plus a pair of identical twins, aged 2-5 years from Italy and the UK, who had newly diagnosed acute lymphoblastic leukaemia. We amplified and sequenced the genomic TEL-AML1 fusion gene with a long-distance inverse PCR method. Primers were designed that could be used in short-range PCR to screen for patient-specific, leukaemia clone-specific TEL-AML1 genomic fusion sequences in neonatal blood spots from each child. Findings. We initially identified TEL-AML1 fusion sequences in blood spots from the identical twins, diagnosed with concordant acute lymphoblastic leukaemia at age 4 years, who shared a single or clonotypic TEL-AML1 sequence that suggested prenatal origin in one twin. Three children were excluded because control genes could not be amplified. Of the other nine patients, six had positive blood spots. Blood spots that were classified as negative were uninformative. Interpretation. Our findings showed that childhood acute lymphoblastic leukaemia is frequently initiated by a chromosome translocation event in utero. Studies in identical twins show however that such an event is insufficient for clinical leukaemia and that a postnatal promotional event is also required.
Articolo in rivista - Articolo scientifico
Burkitt Lymphoma; Child, Preschool; Core Binding Factor Alpha 2 Subunit; Diseases in Twins; Humans; Infant; Infant, Newborn; Neoplasm Proteins; Reverse Transcriptase Polymerase Chain Reaction; Translocation, Genetic; Genetic Predisposition to Disease; Oncogene Proteins, Fusion;
English
1999
354
9189
1499
1503
none
Wiemels, J., Cazzaniga, G., Daniotti, M., Eden, O., Addison, G., Masera, G., et al. (1999). Prenatal origin of acute lymphoblastic leukaemia in children. THE LANCET, 354(9189), 1499-1503 [10.1016/S0140-6736(99)09403-9].
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/363128
Citazioni
  • Scopus 543
  • ???jsp.display-item.citation.isi??? 466
Social impact