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Janus kinase mutations in the development of acute megakaryoblastic leukemia in children with and without Down's syndrome

Leukemia volume 21, pages 1584–1587 (2007)Cite this article

Children with Down's syndrome (DS) have a 20–40-fold increased risk of acute myeloid leukemia (AML). The unique type of AML in DS is referred to as myeloid leukemia of Down's syndrome (ML-DS),1 which is characterized by the frequent occurrence of acute megakaryoblastic leukemia (AMKL or FAB M7-like), a low diagnostic white blood cell count (WBC), young age and excellent outcome when reduced-intensity chemotherapy is applied.2 Approximately 10% of the infants with DS exhibit a postnatal megakaryocytosis syndrome commonly called transient myeloproliferative disorder (TMD) or transient leukemia, which resolves spontaneously in the majority of the cases. Subsequently, approximately 20% of neonates with TMD develop ML-DS within the first 4 years of life.

Acquired mutations in the gene encoding for the major hematopoietic transcription factor GATA1 have been identified in leukemic blasts from virtually all patients with ML-DS and TMD, leading to the exclusive expression of a truncated GATA1 protein (GATA1s). Recently, two studies reported that GATA1s is insufficient to induce leukemia in the absence of other cooperating factors on the background of trisomy 21.3, 4 Furthermore, little is known about the leukemogenesis of AMKL in children without DS (non-DS AMKL). In childhood non-DS AMKL, the t(1;22)(p13;q13) translocation encoding the OTT-MAL (RBM15-MKL1) fusion protein is frequently found.

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Authors and Affiliations

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

    J H Klusmann, K Hahlen, M M van den Heuvel-Eibrink & C M Zwaan

  2. Department of Pediatric Hematology and Oncology, Medical School Hannover, Hannover, Germany

    J H Klusmann & D Reinhardt

  3. Department of Pediatrics, Aarhus University Hospital Skejby, Aarhus, Denmark

    H Hasle

  4. Department of Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, The Netherlands

    G J Kaspers

  5. Department of Pediatric Hematology and Oncology, University Children's Hospital, Muenster, Germany

    U Creutzig

  6. Dutch Childhood Oncology Group, The Hague, The Netherlands. E-mail: c.m.zwaan@erasmusmc.nl,

    K Hahlen

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  1. J H Klusmann
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  8. C M Zwaan
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Klusmann, J., Reinhardt, D., Hasle, H. et al. Janus kinase mutations in the development of acute megakaryoblastic leukemia in children with and without Down's syndrome. Leukemia 21, 1584–1587 (2007). https://doi.org/10.1038/sj.leu.2404694

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