title: A murine model of acute myeloid leukemia with Evi1 overexpression and autocrine stimulation by an intracellular form of GM-CSF in DA-3 cells.
abstract: The poor treatment response of acute myeloid leukemia (AML) overexpressing high-risk oncogenes such as EVI1, demands specific animal models for new treatment evaluations. Evi1 is a common site of activating integrations in murine leukemia virus (MLV)-induced AML and in retroviral and lentiviral gene-modified HCS. Still, a model of overt AML induced by Evi1 has not been generated. Cell lines from MLV-induced AML are growth factor-dependent and non-transplantable. Hence, for the leukemia maintenance in the infected animals, a growth factor source such as chronic immune response has been suggested. We have investigated whether these leukemias are transplantable if provided with growth factors. We show that the Evi1(+)DA-3 cells modified to express an intracellular form of GM-CSF, acquired growth factor independence and transplantability and caused an overt leukemia in syngeneic hosts, without increasing serum GM-CSF levels. We propose this as a general approach for modeling different forms of high-risk human AML using similar cell lines.
authors.affiliation: a Department of Laboratory Medicine , Clinical Research Center, Karolinska Institutet , Huddinge , Sweden.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Cardona
authors.affiliation: a Department of Laboratory Medicine , Clinical Research Center, Karolinska Institutet , Huddinge , Sweden.
authors.forename: Oscar E
authors.initials: OE
authors.lastname: Simonson
authors.affiliation: a Department of Laboratory Medicine , Clinical Research Center, Karolinska Institutet , Huddinge , Sweden.
authors.forename: Iulian I
authors.initials: II
authors.lastname: Oprea
authors.affiliation: a Department of Laboratory Medicine , Clinical Research Center, Karolinska Institutet , Huddinge , Sweden.
authors.forename: Pedro M D
authors.initials: PM
authors.lastname: Moreno
authors.affiliation: b Departament of Basic Science, Medical School, Universidad Industrial de Santander , Colombia.
authors.forename: Maria F
authors.initials: MF
authors.lastname: Silva-Lara
authors.affiliation: a Department of Laboratory Medicine , Clinical Research Center, Karolinska Institutet , Huddinge , Sweden.|e Environmental and Life Sciences, Faculty of Science, Universiti Brunei Darussalam , Negara Brunei Darussalam , Brunei.
authors.forename: Abdalla J
authors.initials: AJ
authors.lastname: Mohamed
authors.affiliation: c Department of Laboratory Medicine , Division of Pathology, Karolinska University Hospital , Huddinge , Sweden.
authors.forename: Birger
authors.initials: B
authors.lastname: Christensson
authors.affiliation: d Department of Medicine , Division of Hematology, Karolinska University Hospital , Huddinge , Sweden.
authors.forename: Gösta
authors.initials: G
authors.lastname: Gahrton
authors.affiliation: d Department of Medicine , Division of Hematology, Karolinska University Hospital , Huddinge , Sweden.
authors.forename: M Sirac
authors.initials: MS
authors.lastname: Dilber
authors.affiliation: a Department of Laboratory Medicine , Clinical Research Center, Karolinska Institutet , Huddinge , Sweden.
authors.forename: C I Edvard
authors.initials: CI
authors.lastname: Smith
authors.affiliation: a Department of Laboratory Medicine , Clinical Research Center, Karolinska Institutet , Huddinge , Sweden.|b Departament of Basic Science, Medical School, Universidad Industrial de Santander , Colombia.
authors.forename: H Jose
authors.initials: HJ
authors.lastname: Arteaga
mesh_terms: D000818:Animals; D019898:Autocrine Communication; D015415:Biomarkers; D001706:Biopsy; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D064596:Isografts; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D000074008:MDS1 and EVI1 Complex Locus Protein; D051379:Mice; D009362:Neoplasm Metastasis; D011519:Proto-Oncogenes / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D047368:Tumor Burden
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C499305:Mecom protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: AML; DA-3 cells; EVI1; GM-CSF; Moloney murine leukemia virus; intracellular cytokines