Figure 1.

Proposed model for the mechanism underlying DS predisposition to megakaryoblastic leukemias. Increased expression of chromosome Hsa21 genes in fetal liver hematopoietic stem cells leads to increased production of megakaryo-erythroid progenitors (MEPs). The somatically acquired GATA1s mutation further blocks megakaryoblastic differentiation and enhances MEPs proliferation. This can lead to transient myeloproliferative disorder (TMD) in 5% of DS newborns. Acquisition of additional somatic genetic or epigenetic events during infancy will lead to the development of full-blown megakaryoblastic leukemia (AMKL) in one-fifth of TMD patients.