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Frequency and prognostic implications of JAK 1-3 aberrations in Down syndrome acute lymphoblastic and myeloid leukemia

Leukemia volume 25, pages 1365–1368 (2011)Cite this article

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Children with Down Syndrome (DS) have an increased risk of developing leukemia, including both acute myeloid (ML-DS) and acute lymphoblastic leukemia (DS ALL).1 These leukemias differ in clinical characteristics and biology from leukemias in non-DS children. ML-DS is characterized by a low diagnostic white blood cell (WBC) count, young age, FAB M7 morphology, excellent clinical outcome with survival rates of >90% and a high sensitivity to chemotherapy in vivo and in-vitro.1, 2 ML-DS is often preceded by transient leukemia (TL) in newborns, which in most cases resolves spontaneously. Approximately 20% of TL patients subsequently develop ML-DS.2 Both the TL and ML-DS blasts are characterized by mutations in the GATA-1 gene, a hematopoietic transcription factor, which result in a truncated protein GATA1s.3 Because these mutations occur both in TL and ML-DS, additional genetic abnormalities are needed in the progression from TL to ML-DS.

DS ALL patients differ from non-DS ALL children. The distribution of favorable prognostic factors in non-DS ALL, such as high hyperdiploidy and ETV6-RUNX1 gene-rearrangements are less frequently found in DS ALL, as well as unfavorable factors such as Philadelphia-chromosome or MLL-rearrangements. Furthermore, the prognosis of DS ALL patients is at best similar and often inferior to that of non-DS ALL patients.4

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Acknowledgements

This work was supported by grants of COG: CA30969, CA29139, CA13539, CA98543 and CA98413.

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Author notes

  1. M Blink and T D Buitenkamp: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatric Oncology/Hematology, Erasmus MC–Sophia Children's Hospital, Rotterdam, The Netherlands

    M Blink, T D Buitenkamp, M M van den Heuvel-Eibrink, A A Danen-van Oorschot, R Pieters & C M Zwaan

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

    V de Haas & R Pieters

  3. Department of Pediatric Oncology/Hematology, AML-BFM Study Group, Medical High School, Hannover, Germany

    D Reinhardt, J-H Klusmann & M Zimmermann

  4. Department of Epidemiology and Health Policy Research, College of Medicine, University of Florida, Gainesville, FL, USA

    M Devidas

  5. Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA

    A J Carroll

  6. Department of Paediatrics, Laboratory of Paediatric Onco-Haematology, University Hospital of Padova, Padova, Italy

    G Basso

  7. Paediatric Oncology and Haematology Unit ‘Lalla Seràgnoli’, University of Bologna, Bologna, Italy

    A Pession

  8. Department of Pediatrics, Nordic Society for Pediatric Hematology and Oncology (NOPHO), Aarhus University Hospital Skejby, Aarhus, Denmark

    H Hasle

  9. Division of Pediatric Hematology/Oncology, Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX, USA

    K R Rabin

  10. Department of Paediatric Haemato-Oncology, Edmond and Lily Safra Children's Hospital, Sheba Medical Centre, Tel-Hashomer, Ramat Gan, and Tel Aviv University Medical School, Tel Aviv, Israel

    S Izraeli

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  1. T D Buitenkamp
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  16. C M Zwaan
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Corresponding author

Correspondence to C M Zwaan.

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The authors declare no conflict of interest.

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Blink, M., Buitenkamp, T., van den Heuvel-Eibrink, M. et al. Frequency and prognostic implications of JAK 1-3 aberrations in Down syndrome acute lymphoblastic and myeloid leukemia. Leukemia 25, 1365–1368 (2011). https://doi.org/10.1038/leu.2011.86

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