Analysis of GATA1 mutations in Down syndrome transient myeloproliferative disorder and myeloid leukemia.
Alford KA., Reinhardt K., Garnett C., Norton A., Böhmer K., von Neuhoff C., Kolenova A., Marchi E., Klusmann J-H., Roberts I., Hasle H., Reinhardt D., Vyas P., International Myeloid Leukemia-Down Syndrome Study Group None.
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.