Deshpande Aniruddha J, Cusan Monica, Rawat Vijay P S, Reuter Hendrik, Krause Alexandre, Pott Christiane, Quintanilla-Martinez Leticia, Kakadia Purvi, Kuchenbauer Florian, Ahmed Farid, Delabesse Eric, Hahn Meinhard, Lichter Peter, Kneba Michael, Hiddemann Wolfgang, Macintyre Elizabeth, Mecucci Cristina, Ludwig Wolf-Dieter, Humphries R Keith, Bohlander Stefan K, Feuring-Buske Michaela, Buske Christian
Department of Medicine III, Klinikum Grosshadern, D-81377 Munich, Germany.
Cancer Cell. 2006 Nov;10(5):363-74. doi: 10.1016/j.ccr.2006.08.023.
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.
在急性髓系白血病（AML）中，开发选择性靶向白血病干细胞的疗法面临的一个挑战是它们与正常造血干细胞（HSC）相似。在这里，我们证明了小鼠CALM/AF10阳性AML中的白血病增殖细胞在B220表面表达和免疫球蛋白重链重排方面与正常HSC不同。此外，白血病移植中B220+细胞的消耗会损害受体中白血病的发展。与小鼠模型一样，人类CALM/AF10阳性AML的特征是CD45RA（B220）阳性、IG DH-JH重排的白血病细胞。这些数据在小鼠白血病模型中表明，AML可由具有淋巴细胞特征的转化祖细胞传播，而这些祖细胞可被不与正常HSC发生交叉反应的抗体靶向。
