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Leukemia in Twins

Prenatal origin of separate evolution of leukemia in identical twins

Leukemia volume 18, pages 1624–1629 (2004)Cite this article

Abstract

Several studies involving identical twins with concordant leukemia and retrospective scrutiny of archived neonatal blood spots have shown that the TEL-AML1 fusion gene in childhood acute lymphoblastic leukemia (ALL) frequently arises before birth. A prenatal origin of childhood leukemia was further supported by the detection of clonotypic immunoglobulin gene rearrangements on neonatal blood spots of children with various other subtypes of ALL. However, no comprehensive study is available linking these clonotypic events. We describe a pair of 5-year-old monozygotic twins with concordant TEL-AML1-positive ALL. Separate leukemic clones were identified in the diagnostic samples since distinct IGH and IGK-Kde gene rearrangements could be detected. Additional differences characterizing the leukemic clones included an aberration of the second, nonrearranged TEL allele observed in one twin only. Interestingly, both the identical TEL-AML1 fusion sequence and distinct immunoglobulin gene rearrangements were identified on the neonatal blood spots indicating that separate preleukemic clones evolved already before birth. Finally, we compared the reported twins with an additional 31 children with ALL by using the microarray technology. Gene expression profiling provided evidence that leukemia in twins harbours the same subtype-typical feature as TEL-AML1-positive leukemia in singletons suggesting that the leukemogenesis model might also be applicable generally.

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Acknowledgements

We are very grateful to Gunnar Cario, Martin Stanulla, and Martin Schrappe from the Hannover Medical School, Germany, for their assistance in sample collecting for the microarray analysis. We also thank the Functional Genomics Center of University and ETH, Zurich, for providing access to the Affymetrix work station. This work was supported by grants from the Krebsliga of the Kanton Zurich, the Krebsliga Schweiz, the ‘Schweizer Forschungsstiftung Kind und Krebs’, and the ‘Provita Kinderleukämiestiftung, Vaduz (FL)’.

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Authors and Affiliations

  1. Department of Oncology, University Children's Hospital, Zurich, Switzerland

    O Teuffel, D R Betts, R Schaub, B W Schäfer & F K Niggli

  2. Seminar for Statistics, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland

    M Dettling

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  1. O Teuffel
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Correspondence to F K Niggli.

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Teuffel, O., Betts, D., Dettling, M. et al. Prenatal origin of separate evolution of leukemia in identical twins. Leukemia 18, 1624–1629 (2004). https://doi.org/10.1038/sj.leu.2403462

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