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Genomic analysis of different clonal evolution in a twin pair with t(12;21) positive acute lymphoblastic leukemia sharing the same prenatal clone

Leukemia volume 22, pages 208–211 (2008)Cite this article

The cryptic translocation t(12;21), with the TEL-AML1 fusion gene, accounts for approximately 25% of childhood B-cell precursor acute lymphoblastic leukemia (ALL) cases. Several studies on monozygotic twins with concordant TEL-AML1-positive ALL have shown that these patients shared common, acquired clonal rearrangements that originated in one twin in utero and diffused to the other twin by a sort of intraplacental metastasis.1, 2

A t(12;21) positive pair of twins was previously reported by Teuffel et al.3 in this journal. In view of their analyses of T-cell receptor (TcR) and immunoglobulin (Ig) gene rearrangements, they concluded that the TEL-AML1 fusion gene occurred before somatic recombination and that separate pre-leukemic clones then evolved independently before birth. We herewith report a female pair of monozygotic twins, aged 3.0 years at concordant diagnosis of ALL, with only 13 days difference in latency. We analyzed the Ig/TcR rearrangements as clonotypic markers to backtrack the common pre-natal pre-leukemic cell shared by the twins. All markers present in both twins at diagnosis must have belonged to the pre-leukemic clone in utero. However, the Ig/TcR rearrangements in our twins suggest a different natural history, with the same Ig/TcR rearrangements being present at diagnosis in both twins, proving that the translocation occurred in a more mature precursor cell which was partially already rearranged, and was then followed by further clonal evolution.

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Acknowledgements

We thank Fondazione Tettamanti, Fondazione Cariplo, AIRC and MIUR for financial support.

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Author notes

  1. R Tussiwand

    Present address: 4Current address: Departement Klinisch-Biologische Wissenschaften (DKBW), Universität Basel, Basel, Switzerland.,

  2. A Biondi and G Cazzaniga: These authors contributed equally to this work.

Authors and Affiliations

  1. Centro Ricerca Tettamanti, Clinica Pediatrica University di Milano Bicocca, Monza, Italy

    S Bungaro, R Tussiwand, C Molteni, M Citterio, A Biondi & G Cazzaniga

  2. Childhood Cancer Research Group, Northern Institute for Cancer Research, University of Newcastle upon Tyne, Newcastle upon Tyne, UK

    J Irving, L Minto & A Hall

  3. Pediatric Hemato-Oncology, Cagliari Hospital, Cagliari, Italy

    R Mura

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  1. S Bungaro
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Correspondence to G Cazzaniga.

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Bungaro, S., Irving, J., Tussiwand, R. et al. Genomic analysis of different clonal evolution in a twin pair with t(12;21) positive acute lymphoblastic leukemia sharing the same prenatal clone. Leukemia 22, 208–211 (2008). https://doi.org/10.1038/sj.leu.2404973

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