Acute myeloid leukemia is propagated by a leukemic stem cell with lymphoid characteristics in a mouse model of CALM/AF10-positive leukemia.
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.
Deshpande
Aniruddha J
AJ
Department of Medicine III, Klinikum Grosshadern, D-81377 Munich, Germany.
Cusan
Monica
M
Rawat
Vijay P S
VP
Reuter
Hendrik
H
Krause
Alexandre
A
Pott
Christiane
C
Quintanilla-Martinez
Leticia
L
Kakadia
Purvi
P
Kuchenbauer
Florian
F
Ahmed
Farid
F
Delabesse
Eric
E
Hahn
Meinhard
M
Lichter
Peter
P
Kneba
Michael
M
Hiddemann
Wolfgang
W
Macintyre
Elizabeth
E
Mecucci
Cristina
C
Ludwig
Wolf-Dieter
WD
Humphries
R Keith
RK
Bohlander
Stefan K
SK
Feuring-Buske
Michaela
M
Buske
Christian
C
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
D015415:Biomarkers; D016177:Macrophage-1 Antigen; D034041:Monomeric Clathrin Assembly Proteins; C439003:PICALM protein, human; D011993:Recombinant Fusion Proteins; D017493:Leukocyte Common Antigens