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Acute Leukemias

Relapsed childhood high hyperdiploid acute lymphoblastic leukemia: presence of preleukemic ancestral clones and the secondary nature of microdeletions and RTK-RAS mutations

Leukemia volume 24, pages 924–931 (2010)Cite this article

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Abstract

Although childhood high hyperdiploid acute lymphoblastic leukemia is associated with a favorable outcome, 20% of patients still relapse. It is important to identify these patients already at diagnosis to ensure proper risk stratification. We have investigated 11 paired diagnostic and relapse samples with single nucleotide polymorphism array and mutation analyses of FLT3, KRAS, NRAS and PTPN11 in order to identify changes associated with relapse and to ascertain the genetic evolution patterns. Structural changes, mainly cryptic hemizygous deletions, were significantly more common at relapse (P<0.05). No single aberration was linked to relapse, but four deletions, involving IKZF1, PAX5, CDKN2A/B or AK3, were recurrent. On the basis of the genetic relationship between the paired samples, three groups were delineated: (1) identical genetic changes at diagnosis and relapse (2 of 11 cases), (2) clonal evolution with all changes at diagnosis being present at relapse (2 of 11) and (3) clonal evolution with some changes conserved, lost or gained (7 of 11), suggesting the presence of a preleukemic clone. This ancestral clone was characterized by numerical changes only, with structural changes and RTK-RAS mutations being secondary to the high hyperdiploid pattern.

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Acknowledgements

This work was supported by grants from the Swedish Childhood Cancer Foundation, the Swedish Cancer Society and the Swedish Research Council.

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Authors and Affiliations

  1. Department of Clinical Genetics, University and Regional Laboratories, Skåne University Hospital, Lund University, Lund, Sweden

    J Davidsson, K Paulsson, D Lindgren, H Lilljebjörn, T Fioretos & B Johansson

  2. Cancer Research UK Medical Oncology Centre, Barts and the London School of Medicine, Queen Mary College, London, UK

    K Paulsson, T Chaplin & B D Young

  3. Department of Clinical Sciences, Pediatrics, University of Umeå, Umeå, Sweden

    E Forestier

  4. Department of Clinical Genetics, Rigshospitalet, Copenhagen, Denmark

    M K Andersen

  5. Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden

    A Nordgren

  6. Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden

    R Rosenquist

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Correspondence to J Davidsson.

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Additional information

Data deposition: The microarray data are deposited in the ArrayExpress repository (http://www.ebi.ac.uk/microarray-as/ae/) with the ID E-MEXP-2333.

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Davidsson, J., Paulsson, K., Lindgren, D. et al. Relapsed childhood high hyperdiploid acute lymphoblastic leukemia: presence of preleukemic ancestral clones and the secondary nature of microdeletions and RTK-RAS mutations. Leukemia 24, 924–931 (2010). https://doi.org/10.1038/leu.2010.39

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