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Various heteroallelic <jats:italic><jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content>2<\/jats:italic> gene mutations are associated with a variety of hematological neoplasms, including myelodysplastic syndromes and leukemias. Here, we report that impaired <jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content>2 expression induces myelodysplastic and myeloproliferative neoplasm development in elderly animals, and this neoplasm resembles chronic myelomonocytic leukemia in humans. <jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content>2 hypomorphic mutant (<jats:italic>G2<\/jats:italic><jats:sup>f<\/jats:sup><jats:styled-content style=\"fixed-case\"><jats:sup>GN<\/jats:sup><\/jats:styled-content><jats:sup>\/<\/jats:sup><jats:styled-content style=\"fixed-case\"><jats:sup>fGN<\/jats:sup><\/jats:styled-content>) mice that were generated by the germline insertion of a neocassette into the <jats:italic>Gata2<\/jats:italic> gene locus avoided the early embryonic lethality observed in <jats:italic>Gata2<\/jats:italic>\u2010null mice. However, adult <jats:italic>G2<\/jats:italic><jats:sup>f<\/jats:sup><jats:styled-content style=\"fixed-case\"><jats:sup>GN<\/jats:sup><\/jats:styled-content><jats:sup>\/<\/jats:sup><jats:styled-content style=\"fixed-case\"><jats:sup>fGN<\/jats:sup><\/jats:styled-content> mice suffered from exacerbated leukocytosis concomitant with progressive anemia and thrombocytopenia and eventually developed massive granulomonocytosis accompanied by trilineage dysplasia. The reconstitution activity of <jats:italic>G2<\/jats:italic><jats:sup>f<\/jats:sup><jats:styled-content style=\"fixed-case\"><jats:sup>GN<\/jats:sup><\/jats:styled-content><jats:sup>\/<\/jats:sup><jats:styled-content style=\"fixed-case\"><jats:sup>fGN<\/jats:sup><\/jats:styled-content> mouse stem cells was impaired. Furthermore, <jats:italic>G2<\/jats:italic><jats:sup>f<\/jats:sup><jats:styled-content style=\"fixed-case\"><jats:sup>GN<\/jats:sup><\/jats:styled-content><jats:sup>\/<\/jats:sup><jats:styled-content style=\"fixed-case\"><jats:sup>fGN<\/jats:sup><\/jats:styled-content> progenitors showed myeloid lineage\u2010biased proliferation and differentiation. Myeloid progenitor accumulation started at a younger age in <jats:italic>G2<\/jats:italic><jats:sup>f<\/jats:sup><jats:styled-content style=\"fixed-case\"><jats:sup>GN<\/jats:sup><\/jats:styled-content><jats:sup>\/<\/jats:sup><jats:styled-content style=\"fixed-case\"><jats:sup>fGN<\/jats:sup><\/jats:styled-content> mice and appeared to worsen with age. <jats:italic>G2<\/jats:italic><jats:sup>f<\/jats:sup><jats:styled-content style=\"fixed-case\"><jats:sup>GN<\/jats:sup><\/jats:styled-content><jats:sup>\/<\/jats:sup><jats:styled-content style=\"fixed-case\"><jats:sup>fGN<\/jats:sup><\/jats:styled-content> mice showed increased expression of transcripts encoding cytokine receptors, such as macrophage colony\u2010stimulating factor receptor and interleukin\u20106 receptor, in granulocyte\u2010monocyte progenitors. This increased expression could be correlated with the hypersensitive granulomonocytic proliferation reaction when the mice were exposed to lipopolysaccharide. Taken together, these observations indicate that <jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content>2 hypomorphism leads to a hyperreactive defense response to infections, and this reaction is attributed to a unique intrinsic cell defect in the regulation of myeloid expansion that increases the risk of hematological neoplasm transformation.<\/jats:p>","DOI":"10.1111\/cas.13959","type":"journal-article","created":{"date-parts":[[2019,2,2]],"date-time":"2019-02-02T13:59:35Z","timestamp":1549115975000},"page":"1183-1193","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["<scp>GATA<\/scp>2 hypomorphism induces chronic myelomonocytic leukemia in mice"],"prefix":"10.1111","volume":"110","author":[{"given":"Nobuhiko","family":"Harada","sequence":"first","affiliation":[{"name":"Department of Molecular Hematology Tohoku University Graduate School of Medicine  Sendai Japan"},{"name":"Department of Laboratory 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Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6672-7606","authenticated-orcid":false,"given":"Ritsuko","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Molecular Hematology Tohoku University Graduate School of Medicine  Sendai Japan"},{"name":"Tohoku Medical Megabank Organization Tohoku University  Sendai 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