Mouse models have demonstrated that both hematopoietic stem cells (HSCs) as well as downstream myeloid progenitors can be targets of transformation in AML. We recently showed in a murine model of the CALM/AF10 fusion gene positive leukemia, that progenitors with lymphoid characteristics can be leukemic stem cell (LSC) candidates in AML. We could demonstrate that the LSC candidate in the CALM/AF10 murine model was positive for the lymphoid associated surface antigen B220, which was not expressed by the leukemic bulk or the normal HSC pool. This offers the intriguing possibility to target the LSCs with antibodies that spare the normal stem cell.