title: Hematopoietic overexpression of the transcription factor Erg induces lymphoid and erythro-megakaryocytic leukemia.
abstract: The transcription factor encoded by the E-twenty-six (ETS)-related gene, ERG, is an essential regulator of hematopoietic stem cell function and a potent human oncoprotein. Enforced expression of ERG in murine hematopoietic cells leads to the development of a well-characterized lymphoid leukemia and a less well-defined non lymphoid disease. To clarify the latter, we generated murine bone marrow chimeras with enforced Erg expression in engrafted hematopoietic progenitor cells. As expected, these mice developed lymphoid leukemia. However, the previously reported non lymphoid disease that developed was shown to be a uniform, transplantable leukemia with both erythroid and megakaryocytic characteristics. In vivo, this disease had the overall appearance of an erythroleukemia, with an accumulation of immature erythroblasts that infiltrated the bone marrow, spleen, liver, and lung. However, when stimulated in vitro, leukemic cell clones exhibited both erythroid and megakaryocytic differentiation, suggesting that transformation occurred in a bipotential progenitor. Thus, in mice, Erg overexpression induces the development of not only lymphoid leukemia but also erythro-megakaryocytic leukemia.
authors.affiliation: Cancer and Hematology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville 3052, VIC, Australia. carmichael@wehi.edu.au
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Carmichael
authors.forename: Donald
authors.initials: D
authors.lastname: Metcalf
authors.forename: Katya J
authors.initials: KJ
authors.lastname: Henley
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Kruse
authors.forename: Ladina
authors.initials: L
authors.lastname: Di Rago
authors.forename: Sandra
authors.initials: S
authors.lastname: Mifsud
authors.forename: Warren S
authors.initials: WS
authors.lastname: Alexander
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Kile
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D019070:Cell Lineage; D004900:Erythroblasts / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006412:Hematopoietic Stem Cells / Q000166:cytology; D007938:Leukemia / Q000235:genetics* / Q000378:metabolism; D007947:Leukemia, Megakaryoblastic, Acute / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D012190:Retroviridae / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG
chemical_list: C531115:ERG protein, mouse; D015513:Oncogene Proteins; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG