title: Dysplastic definitive hematopoiesis in AML1/EVI1 knock-in embryos.
abstract: The AML1/EVI1 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/EVI1 chimeric gene into mouse Aml1 genomic locus to explore its effect in developmental hematopoiesis in vivo. AML1/EVI1/+ embryo showed defective hematopoiesis in the fetal liver and died around embryonic day 13.5 (E13.5) as a result of hemorrhage in the central nervous system. The peripheral blood had yolk-sac-derived nucleated erythroblasts but lacked erythrocytes of the definitive origin. Although E12.5 fetal liver contained progenitors for macrophage only, E13.5 fetal liver contained multilineage progenitors capable of differentiating into dysplastic myelocyte and megakaryocyte. No erythroid progenitor was detected in E12.5 or E13.5 fetal liver. Hematopoietic progenitors from E13.5 AML1/EVI1/+ fetal liver were highly capable of self-renewal compared with those 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/EVI1/+ fetal liver.
authors.affiliation: Department of Hematology, Dokkyo University School of Medicine, 880 Kitakobayashi, Mibu-machi, Shimotsuga-gun, Tochigi 321-0293, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Maki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yamagata
authors.forename: Takashi
authors.initials: T
authors.lastname: Asai
authors.forename: Ieharu
authors.initials: I
authors.lastname: Yamazaki
authors.forename: Hideaki
authors.initials: H
authors.lastname: Oda
authors.forename: Hisamaru
authors.initials: H
authors.lastname: Hirai
authors.forename: Kinuko
authors.initials: K
authors.lastname: Mitani
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000235:genetics; D004622:Embryo, Mammalian; D004900:Erythroblasts; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D020300:Intracranial Hemorrhages / Q000209:etiology; D060588:LIM Domain Proteins; D008099:Liver / Q000166:cytology / Q000196:embryology; D000074008:MDS1 and EVI1 Complex Locus Protein; D008667:Metalloproteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011519:Proto-Oncogenes / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; D008667:Metalloproteins; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1; C504411:AML1-EVI1 fusion protein, human; C513188:Lmo2 protein, mouse; C499305:Mecom protein, mouse; C493726:Runx1 protein, mouse