Abstract
Children with Down syndrome (DS) have an approximately 20-fold higher incidence of leukemia than unaffected children, and most leukemia cases with DS present as acute megakaryocytic leukemia (AMKL). At least 10% of neonates with DS develop transient myeloproliferative disorder (TMD), and 20% to 30% of patients with TMD develop AMKL. Mutations in the GATA1 gene are identified not only in AMKL patients but also in TMD patients; however, sequential analysis of GATA1 is not often performed in the same patients. We describe a child with DS who developed TMD followed by AMKL and have identified different mutations in the GATA1 gene during the course of TMD and AMKL. Distinct clones were associated with the development of TMD and AMKL in this patient.
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References
Lange B. The management of neoplastic disorders of haematopoiesis in children with Down’s syndrome. BrJ Haematol. 2000;110:512–524.
Zipursky A. Transient leukaemia: a benign form of leukaemia in newborn infants with trisomy 21. Br J Haematol. 2003;120:930–938.
Hayashi Y, Eguchi M, Sugita K, et al. Cytogenetic findings and clinical features in acute leukemia and transient myeloproliferative disorder in Down’s syndrome. Blood. 1998;72:15–23.
Lu G, Altman AJ, Ben PA. Review of the cytogenetic changes in acute megakaryocytic leukemia. Cancer Genet Cytogenet. 1993;67:81–89.
Tsai SF, Martin DI, Zon LI, D’Andrea AD, Wong GG, Orkin SH. Cloning of cDNA for the major DNA-binding protein of the erythroid lineage through expression in mammalian cells. Nature. 1989;339:446–451.
Martin DI, Zon LI, Mutter G, Orkin SH. Expression of an erythroid transcription factor in megakaryocytic and mast cell lineages. Nature. 1990;344:444–447.
Romeo PH, Prandini MH, Joulin V, et al. Megakaryocytic and erythroid lineages share specific transcription factors. Nature. 1990;344:447–449.
Zon LI, Yamaguchi Y, Yee K, et al. Expression of mRNA for the GATA-binding proteins in human eosinophils and basophils: potential role in gene transcription. Blood. 1993;81:3234–3241.
Wechsler J, Greene M, McDevitt MA, et al. Acquired mutations in GATA1 in the megakaryoblastic leukemia of Down syndrome. Nat Genet. 2002;32:148–152.
Mundschau G, Gurbuxani S, Gamis AS, Greene ME, Arceci RJ, Crispino JD. Mutagenesis of GATA1 is an initiating event in Down syndrome leukemogenesis. Blood. 2003;101:4298–4300.
Groet J, McElwaine S, Spinelli M, et al. Acquired mutations in GATA1 in neonates with Down’s syndrome with transient myeloid disorder. Lancet. 2003;361:1617–1620.
Xu G, Nagano M, Kanezaki R, et al. Frequent mutations in the GATA-1 gene in the transient myeloproliferative disorder of Down syndrome. Blood. 2003;102:2960–2968.
Cantor AB. GATA transcription factors in hematopoietic disease. Int J Hematol. 2005;81:378–384.
Rainis L, Bercovich D, Strehl S, et al. Mutations in exon 2 of GATA1 are early events in megakaryocytic malignancies associated with trisomy 21. Blood. 2003;102:981–986.
Hitzler JK, Cheung J, Li Y, Scherer SW, Zipursky A. GATA1 mutations in transient leukemia and acute megakaryoblastic leukemia of Down syndrome. Blood. 2003;101:4301–4304.
Shimada A, Xu G, Toki T, Kimura H, Hayashi Y, Ito E. Fetal origin of the GATA1 mutation in identical twins with transient myeloproliferative disorder and acute megakaryocytic leukemia accompanying Down syndrome. Blood. 2004;103:366.
Xu G, Kato K, Toki T, Takahashi Y, Terui K, Ito E. Development of acute megakaryocytic leukemia from a minor clone in a Down syndrome patient with clinically overt transient myeloproliferative disorder. J Pediatr Hematol Oncol. 2006;28:696–698.
Calligaris R, Bottardi S, Cogoi S, et al. Alternative translation initiation site usage results in two functionally distinct forms of the GATA-1 transcription factor. Proc Natl Acad Sci USA. 1995;92:11598–11602.
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Kanegane, H., Watanabe, S., Nomura, K. et al. Distinct Clones are Associated with the Development of Transient Myeloproliferative Disorder and Acute Megakaryocytic Leukemia in a Patient with Down Syndrome. Int J Hematol 86, 250–252 (2007). https://doi.org/10.1532/IJH97.07058
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DOI: https://doi.org/10.1532/IJH97.07058