title: Acute myeloid leukemia is propagated by a leukemic stem cell with lymphoid characteristics in a mouse model of CALM/AF10-positive leukemia.
abstract: A challenge for the development of therapies selectively targeting leukemic stem cells in acute myeloid leukemia (AML) is their similarity to normal hematopoietic stem cells (HSCs). Here we demonstrate that the leukemia-propagating cell in murine CALM/AF10-positive AML differs from normal HSCs by B220 surface expression and immunoglobulin heavy chain rearrangement. Furthermore, depletion of B220+ cells in leukemic transplants impaired development of leukemia in recipients. As in the murine model, human CALM/AF10-positive AML was characterized by CD45RA (B220)-positive, IG DH-JH rearranged leukemic cells. These data demonstrate in a murine leukemia model that AML can be propagated by a transformed progenitor with lymphoid characteristics, which can be targeted by antibodies that do not crossreact with normal HSCs.
authors.affiliation: Department of Medicine III, Klinikum Grosshadern, D-81377 Munich, Germany.
authors.forename: Aniruddha J
authors.initials: AJ
authors.lastname: Deshpande
authors.forename: Monica
authors.initials: M
authors.lastname: Cusan
authors.forename: Vijay P S
authors.initials: VP
authors.lastname: Rawat
authors.forename: Hendrik
authors.initials: H
authors.lastname: Reuter
authors.forename: Alexandre
authors.initials: A
authors.lastname: Krause
authors.forename: Christiane
authors.initials: C
authors.lastname: Pott
authors.forename: Leticia
authors.initials: L
authors.lastname: Quintanilla-Martinez
authors.forename: Purvi
authors.initials: P
authors.lastname: Kakadia
authors.forename: Florian
authors.initials: F
authors.lastname: Kuchenbauer
authors.forename: Farid
authors.initials: F
authors.lastname: Ahmed
authors.forename: Eric
authors.initials: E
authors.lastname: Delabesse
authors.forename: Meinhard
authors.initials: M
authors.lastname: Hahn
authors.forename: Peter
authors.initials: P
authors.lastname: Lichter
authors.forename: Michael
authors.initials: M
authors.lastname: Kneba
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hiddemann
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Macintyre
authors.forename: Cristina
authors.initials: C
authors.lastname: Mecucci
authors.forename: Wolf-Dieter
authors.initials: WD
authors.lastname: Ludwig
authors.forename: R Keith
authors.initials: RK
authors.lastname: Humphries
authors.forename: Stefan K
authors.initials: SK
authors.lastname: Bohlander
authors.forename: Michaela
authors.initials: M
authors.lastname: Feuring-Buske
authors.forename: Christian
authors.initials: C
authors.lastname: Buske
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002471:Cell Transformation, Neoplastic; D004195:Disease Models, Animal; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000503:physiopathology*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000378:metabolism; D051379:Mice; D034041:Monomeric Clathrin Assembly Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate
chemical_list: D015415:Biomarkers; D016177:Macrophage-1 Antigen; D034041:Monomeric Clathrin Assembly Proteins; C439003:PICALM protein, human; D011993:Recombinant Fusion Proteins; D017493:Leukocyte Common Antigens