Proposed model for the mechanism for the leukemogenic cooperation between constitutional trisomy 21 (cT21) and GATA1s mutations in the megakaryoblastic leukemias of DS.5 Increased expression of genes from cT21 in fetal liver HPCs tilt the normal hematopoiesis toward increased production of megakaryocytic erythroid progenitors (MEPs). It's also possible that cT21 blocks terminal megakaryocytic (MK) differentiation. The somatically-acquired GATA1s mutation further blocks MK differentiation and enhances the proliferation of the MEPs. Professional illustration by Alice Y. Chen.
