Analysis of GATA1 mutations in Down syndrome transient myeloproliferative disorder and myeloid leukemia

• Published in: Blood 2011-08, Vol.118 (8), p.2222-2238
• Main Authors: Alford, Kate A., Reinhardt, Katarina, Garnett, Catherine, Norton, Alice, Böhmer, Katarina, von Neuhoff, Christine, Kolenova, Alexandra, Marchi, Emanuele, Klusmann, Jan-Henning, Roberts, Irene, Hasle, Henrik, Reinhardt, Dirk, Vyas, Paresh
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Child, Preschool; Chromosome aberrations; DNA Mutational Analysis; Down Syndrome - complications; Down Syndrome - genetics; Female; GATA1 Transcription Factor - genetics; Genetic Testing; Hematologic and hematopoietic diseases; Humans; Infant; Infant, Newborn; Leukemia, Myeloid - complications; Leukemia, Myeloid - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical genetics; Medical sciences; Mutation; Myeloproliferative Disorders - complications; Myeloproliferative Disorders - genetics; Prognosis
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2011-03-342774

Children with Down syndrome (DS) up to the age of 4 years are at a 150-fold excess risk of developing myeloid leukemia (ML-DS). Approximately 4%-5% of newborns with DS develop transient myeloproliferative disorder (TMD). Blast cell structure and immunophenotype are similar in TMD and ML-DS. A mutation in the hematopoietic transcription factor GATA1 is present in almost all cases. Here, we show that simple techniques detect GATA1 mutations in the largest series of TMD (n = 134; 88%) and ML-DS (n = 103; 85%) cases tested. Furthermore, no significant difference in the mutational spectrum between the 2 disorders was seen. Thus, the type of GATA1 sequence mutation is not a reliable tool and is not prognostic of which patients with TMD are probable to develop ML-DS.