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تسجيل

Down Syndrome–Associated Acute Myeloid Leukemia

المؤلف:  Hoffman, R., Benz, E. J., Silberstein, L. E., Heslop, H., Weitz, J., & Salama, M. E.

المصدر:  Hematology : Basic Principles and Practice

الجزء والصفحة:  8th E , P859

2026-09-03

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The myeloid leukemia of DS was given a special WHO subclassification (ML-DS) because of its unique clinical and biologic features. These erythromegakaryoblastic leukemias are diagnosed before the age of 5 years and often present with thrombocytopenia and/or myelodysplasia. ML-DS is always preceded by the neo natal preleukemic syndrome, transient abnormal myelopoiesis (TAM; also known as transient MPD) that may, or may not, be clinically apparent. Unlike acute megakaryoblastic leukemias in patients without DS, these patients usually respond well to therapy with most patients being cured. Genetically, ML-DS is characterized by an acquired mutation in the GATA1 gene (90%). The mutation in GATA1 is necessary but insufficient for development of ML-DS. Virtually all cases of TAM and ML-DS have N-terminal truncating GATA1 mutations. GATA1 mutations are present at birth in both neonates with DS with TAM and, through retrospective analysis of neonatal blood spots, also in children with ML-DS without a previous history of TAM. It is not clear at what stage in fetal development GATA1 mutations arise; the earliest point in gestation at which mutations have been identified is 21 weeks. GATA1 mutations disappear when TAM (or ML-DS) enters remission, indicating that they are acquired.