Acute myeloid leukemia is propagated by a leukemic stem cell with lymphoid characteristics in a mouse model of CALM/AF10-positive leukemia
Copyright policy )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.
- University of Perugia Italy
- Pathologisches Institut Germany
- University Hospital Schleswig-Holstein Germany
- University of British Columbia Canada
- Necker-Enfants Malades Hospital France
Cancer Research, Recombinant Fusion Proteins, HUMDISEASE, Macrophage-1 Antigen, Cell Biology, Hematopoietic Stem Cells, Survival Rate, Disease Models, Animal, Leukemia, Myeloid, Acute, Mice, Cell Transformation, Neoplastic, Oncology, Monomeric Clathrin Assembly Proteins, Animals, Humans, Leukocyte Common Antigens, Biomarkers, Bone Marrow Transplantation
Cancer Research, Recombinant Fusion Proteins, HUMDISEASE, Macrophage-1 Antigen, Cell Biology, Hematopoietic Stem Cells, Survival Rate, Disease Models, Animal, Leukemia, Myeloid, Acute, Mice, Cell Transformation, Neoplastic, Oncology, Monomeric Clathrin Assembly Proteins, Animals, Humans, Leukocyte Common Antigens, Biomarkers, Bone Marrow Transplantation
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