Dysplastic definitive hematopoiesis in AML1/Evi-1 knock-in embryos.

Posted by rob on May 27, 2005 under Uncategorized | Be the First to Comment

Maki K, Yamagata T, Asai T, Yamazaki I, Oda H, Hirai H, Mitani K

Blood. 2005 May 24;

The AML1/Evi-1 chimeric gene is created by the t(3;21)(q26;q22) chromosomal translocation seen in patients with leukemic transformation of myelodysplastic syndrome or blastic crisis of chronic myelogenous leukemia. We knocked-in the AML1/Evi-1 chimeric gene into mouse AML1 genomic locus to explore its effect in developmental hematopoiesis in vivo. AML1/Evi-1/+ embryo showed defective hematopoiesis in the fetal liver, and died around E13.5 due to hemorrhage in the central nervous system. The peripheral blood had yolk sac-derived nucleated erythroblasts but lacked erythrocytes of the definitive origin. While E12.5 fetal liver contained progenitors for macrophage only, E13.5 fetal liver contained multi-lineage progenitors capable of differentiating into dysplastic myelocyte and megakaryocyte. No erythroid progenitor was detected in E12.5 or E13.5 fetal liver. Hematopoietic progenitor from E13.5 AML1/Evi-1/+ fetal liver was highly self-renewal compared to that from wild-type liver. Maintained expression of PU.1 gene and decreased expression of LMO2 and SCL genes may explain the aberrant hematopoiesis in AML1/Evi-1/+ fetal liver.

Dysplastic definitive hematopoiesis in AML1/Evi-1 knock-in embryos.