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Circulating t(2;5)-positive cells can be detected in cord blood of healthy newborns

Leukemia volume 26, pages 188–190 (2012)Cite this article

Several studies have demonstrated the presence of lymphoma-associated chromosomal translocations in blood samples of healthy adults using sensitive reverse transcription-PCR (RT-PCR) assays. The t(14;18) translocation (Bcl-2-IgH), which is the most common genetic aberration in lymphoid malignancies (90% in follicular lymphoma and 20–30% in diffuse large B-cell lymphomas), is found in circulating cells in up to 60% of healthy individuals by very sensitive PCR techniques. Furthermore, several studies clearly showed an age-dependent increase in the prevalence of circulating t(14;18)-positive cells that could be related to the environmental exposure to carcinogens, pesticides and excessive smoking. Similarly, BCR–ABL sequences derived from the t(9;22) Philadelphia translocation could be demonstrated in healthy persons.

The t(2;5)(p23;q35) is one of the most common cytogenetic abnormalities in Anaplastic Lymphoma Kinase (ALK)-positive anaplastic large cell lymphoma (ALCL).1 This translocation results in fusion of the genomic DNA of two genes, NPM on chromosome 5 and ALK on chromosome 2. This leads to the NPM–ALK fusion gene on the derivative chromosome 5, and to transcription of the chimeric NPM–ALK fusion gene. Translocation involving the ALK gene is found in 90% of paediatric ALCL cases2 but only in 55% of adult ALCL,3 raising the hypothesis that this chromosomal abnormality might occur in utero. Previous studies already demonstrated that healthy adults carried NPM–ALK-positive cells in peripheral blood and NPM–ALK-negative tissues.4, 5 However, their presence has never been investigated in healthy newborns. Here we report the prevalence and the level of NPM–ALK transcripts in a series of 103 umbilical cord blood samples obtained from healthy newborns, using a real-time quantitative-PCR (RQ-PCR) approach that enabled us to detect circulating NPM–ALK-positive cells with a sensitivity of 10−5 (see Supplementary Information for more detailed information). NPM–ALK transcripts were demonstrated in 2 of 103 analysed cord blood samples, which is a prevalence of 1.95%. The normalized copy numbers (NCNs) being expressed as copy numbers of NPM–ALK per 104 copies ABL, between two and six NCNs, were detected in the two PCR-positive samples. Blind re-checking test by another laboratory (C. Damm-Welk, Germany) was applied to these two positive cases along with 11 negative ones and gave concordant results.

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Acknowledgements

This study was supported by the ‘Projet Hospitalier de Recherche Clinique’ (Institut National du Cancer, France). We thank Jeannine Boyes for her technical assistance.

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Author notes

  1. C Laurent and C Lopez: First co-authors.

Authors and Affiliations

  1. Université Paul-Sabatier, Toulouse, France

    C Laurent, G Delsol, P Brousset & L Lamant

  2. Laboratoire d’Anatomie Pathologique, CHU Purpan, Place Baylac, Toulouse, France

    C Laurent, C Lopez, G Delsol, P Brousset & L Lamant

  3. CRCT, INSERM UMR 1037, Toulouse, France

    C Desjobert, P Brousset & L Lamant

  4. Fédération de Gynécologie-Obstétrique, CHU Paule de Viguier, Toulouse, France

    A Berrebi

  5. Department of Pediatric Hematology and Oncology, Justus-Liebig-University, Giessen, Germany

    C Damm-Welk

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  1. C Laurent
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  2. C Lopez
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  3. C Desjobert
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  8. L Lamant
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Correspondence to L Lamant.

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Supplementary Information accompanies the paper on the Leukemia website

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Laurent, C., Lopez, C., Desjobert, C. et al. Circulating t(2;5)-positive cells can be detected in cord blood of healthy newborns. Leukemia 26, 188–190 (2012). https://doi.org/10.1038/leu.2011.209

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