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Acute Leukemias

High concordance of subtypes of childhood acute lymphoblastic leukemia within families: lessons from sibships with multiple cases of leukemia

Leukemia volume 26, pages 675–681 (2012)Cite this article

Abstract

Polymorphic genes have been linked to the risk of acute lymphoblastic leukemia (ALL). Surrogate markers for a low burden of early childhood infections are also related to increased risk for developing childhood ALL. It remains uncertain, whether siblings of children with ALL have an increased risk of developing ALL. This international collaboration identified 54 sibships with two (N=51) or more (N=3) cases of childhood ALL (ages <18 years). The 5-year event-free survival for 61 patients diagnosed after 1 January 1990 was 0.83±0.05. Ages at diagnosis (Spearman correlation coefficient, rS=0.41, P=0.002) were significantly correlated, but not WBCs (rS=0.23, P=0.11). In 18 sibships with successful karyotyping in both cases, six were concordant for high-hyperdiploidy (N=3), t(12;21) [ETV6/RUNX1] (N=1), MLL rearrangement (N=1) or t(1;19)(q23/p13) (N=1). Eleven sibships were ALL-subtype concordant, being T-cell ALL (T-ALL) (N=5, of a total of six sibships, where the first-born had T-ALL) or B-lineage ALL belonging to the same cytogenetic subset (N=6), a finding that differs significantly from the expected chance distribution (κ: 0.58; P<0.0001). These data indicate strong genetic and/or environmental risk factors for childhood ALL that are restricted to specific ALL subtypes, which must be taken into account, when performing epidemiological studies to reveal etiological factors.

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Acknowledgements

We thank our international collaborators who have provided information on the individual sibships: Roland A Ammann, Bern, Switzerland; Patricia Andersson, Westmead, Australia; K Arjmandi, Tehran, Iran; Mikael Behrendtz, Linköping, Sweden; Yves Bertrand, Lyon, France; Tim Eden, Manchester, United Kigdom; Cecile Galzy, Montpellier, France; Kaizo Horibe, Nagoya, Japan; Liisa Hovi, Helsinki, Finland; Dragana Janic, Belgrade, Serbia; Gritta Janka-Schaub, Hamburg, Germany; Pam Kearns, Birmingham, United Kingdom; Razeena Khan, London United Kingdom; Sverre Lie, Oslo, Norway; Gudmar Lönnerholm, Uppsala, Sweden; Michael Madden, Cork, Ireland; Ruben Mayo, Santa Fe, Argentina; Andrea Pession, Bologna, Italy; Kim Ritchey, Pittsburg, USA; Henrik Schrøder, Skejby, Denmark; Lewis Silverman, Boston, USA; Martin Stanulla, Kiel, Germany; Martha Vizcaino, Bogota, Colombia; Nancy Youngren, Minnesota, USA; Jeanette Winther, Copenhagen, Denmark. This study has received financial support from the Childhood Cancer Foundation, Denmark; the University Hospital Rigshospitalet; Michael Goldschmidt Holding A/S; the Otto Christensen Foundation and the US National Institutes of Health Grant P30 CA21765; and the American Lebanese Syrian Associated Charities (ALSAC). Kjeld Schmiegelow holds the Childhood Cancer Foundation Research Professorship in Pediatric Oncology.

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Authors and Affiliations

  1. Pediatric Clinics, The Juliane Marie Centre, The University Hospital Rigshospitalet, Copenhagen, Denmark

    K Schmiegelow & U Lausten Thomsen

  2. The Faculty of Medicine, Institute of Gynecology, Obstetrics and Pediatrics, The University of Copenhagen, Copenhagen, Denmark

    K Schmiegelow

  3. Department of Pediatric Hematology-Immunology, Hopital Robert Debré, Paris, France

    A Baruchel

  4. Hematooncology Department, Hospital Infantil Manuel de Jesus Rivera, Managua, Nicaragua

    C E Pacheco

  5. Department of Pediatric Oncology, ErasmusMC-Sophia Children’s Hospital, Rotterdam, The Netherlands

    Rob Pieters

  6. Dutch Childhood Oncology Group, The Hague, The Netherlands

    Rob Pieters

  7. Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional de Cancer, Rio de Janeiro, Brazil

    M S Pombo-de-Oliveira

  8. Department of Biostatistics, The University of Copenhagen, Copenhagen, Denmark

    E W Andersen

  9. Department of Epidemiological Research, Statens Serum Institut, Copenhagen, Denmark

    K Rostgaard & H Hjalgrim

  10. Department of Oncology, St Jude Children’s Research Hospital, Memphis, TN, USA

    C-H Pui

  11. University of Tennessee Health Science Center, Memphis, TN, USA

    C-H Pui

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  1. K Schmiegelow
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Correspondence to K Schmiegelow.

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Author contributions

Kjeld Schmiegelow designed the study, scrutinized the literature, collected and analyzed the data, and wrote the manuscript. Ulrik Lausten-Thomsen scrutinized the literature. Andre Baruchel, Carlo E Pacheco, Rob Pieters, Maria S Pombo-de-Oliveira and Ching-Hon Pui accrued patient data. Elisabeth Wreford Andersen, Klaus Rostgaard and Henrik Hjalgrim analyzed the data. All authors commented and approved the final manuscript.

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Schmiegelow, K., Lausten Thomsen, U., Baruchel, A. et al. High concordance of subtypes of childhood acute lymphoblastic leukemia within families: lessons from sibships with multiple cases of leukemia. Leukemia 26, 675–681 (2012). https://doi.org/10.1038/leu.2011.274

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