23 de enero de 2012

GATA1 mutations in transient leukemia and acute megakaryoblastic leukemia of Down syndrome


Blood, 1 June 2003, Vol. 101, No. 11, pp. 4301-4304


CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Brief report

GATA1 mutations in transient leukemia and acute megakaryoblastic leukemia of Down syndrome

Johann K. Hitzler, Joseph Cheung, Yue Li, Stephen W. Scherer, and Alvin Zipursky
From the Department of Pediatrics, Division of Hematology/Oncology, and the Program in Developmental Biology, Program in Genetics and Genomic Biology, Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada; and the Department of Molecular and Medical Genetics, University of Toronto, Toronto, ON, Canada.
Children with constitutional trisomy 21 (Down syndrome) have an approximately 500-fold increased risk of developing acute megakaryoblastic leukemia (AMKL), a form of acute myeloid leukemia. Unique to newborn infants with Down syndrome is a transient leukemia (TL), also referred to as transient myeloproliferative syndrome, that undergoes spontaneous remission in the majority of cases but in approximately 20% is followed by AMKL later in life. Recently mutations of the gene encoding the hematopoietic transcription factor GATA1 were shown to be specific for AMKL of Down syndrome. Here, we demonstrate that GATA1 mutations are present in blasts of TL and show the identical GATA1 mutation in sequential samples collected from a patient during TL and subsequent AMKL. These findings suggest a model of malignant transformation in Down syndrome AMKL in which GATA1 mutations are an early event and AMKL arises from latent TL clones following initial apparent remission.