title: Modeling de novo leukemogenesis from human cord blood with MN1 and NUP98HOXD13.
abstract: Leukemic transformation of human cells is a complex process. Here we show that forced expression of MN1 in primitive human cord blood cells maintained on stromal cells in vitro induces a transient, but not serially transplantable, myeloproliferation in engrafted mice. However, cotransduction of an activated HOX gene (NUP98HOXD13) with MN1 induces a serially transplantable acute myeloid leukemia (AML). Further characterization of the leukemic cells generated from the dually transduced cells showed the activation of stem cell gene expression signatures also found in primary human AML. These findings show a new forward genetic model of human leukemogenesis and further highlight the relevance of homeobox transcription factors in the transformation process.
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada;
authors.forename: Suzan
authors.initials: S
authors.lastname: Imren
authors.affiliation: Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany;
authors.forename: Michael
authors.initials: M
authors.lastname: Heuser
authors.affiliation: Division of Hematology, Hematologic Malignancies, University of Colorado AMC, Aurora, CO;
authors.forename: Maura
authors.initials: M
authors.lastname: Gasparetto
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada;
authors.forename: Philip A
authors.initials: PA
authors.lastname: Beer
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada;
authors.forename: Gudmundur L
authors.initials: GL
authors.lastname: Norddahl
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada;
authors.forename: Ping
authors.initials: P
authors.lastname: Xiang
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada;
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Medicine, Hematology and Oncology, University of Frankfurt, Frankfurt/Main, Germany;
authors.forename: Tobias
authors.initials: T
authors.lastname: Berg
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada;
authors.forename: Garrett W
authors.initials: GW
authors.lastname: Rhyasen
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada;
authors.forename: Patricia
authors.initials: P
authors.lastname: Rosten
authors.affiliation: Department of Pathology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea;
authors.forename: Gyeongsin
authors.initials: G
authors.lastname: Park
authors.affiliation: Department of Laboratory Medicine, Medical School of Inha University, Incheon, Korea; and.
authors.forename: Yeonsook
authors.initials: Y
authors.lastname: Moon
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada;
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Weng
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada;
authors.forename: Connie J
authors.initials: CJ
authors.lastname: Eaves
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: R Keith
authors.initials: RK
authors.lastname: Humphries
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005312:Fetal Blood / Q000378:metabolism*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C506524:MN1 protein, human; C521093:NUP98-HOXD13 protein, human; D015514:Oncogene Proteins, Fusion; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins