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Mixed Lineage Leukemia Translocations and a Leukemia Stem Cell Program

Division of Hematology/Oncology, Children's Hospital, Department of Pediatric Oncology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, Massachusetts

Requests for reprints: Scott A. Armstrong, Children's Hospital Boston, Karp Family Research Laboratories, 1 Blackfan Circle, Boston, MA 02115. Phone: 617-919-2508; Fax: 617-730-0934; E-mail: Scott.Armstrong{at}childrens.harvard.edu.

Cancer stem cells (CSC) may provide the self-renewal capacity required to sustain a tumor. One possibility is that CSC arise from the stem cell counterparts in normal tissues. Alternatively, CSC may arise from more differentiated progenitor cells found in certain tissues. In support of this idea, we showed recently that mixed lineage leukemia fusion oncoproteins can convert committed hematopoietic progenitors into leukemias, which include leukemia stem cells expressing a self-renewal associated program in the context of a differentiated myeloid cell. The findings suggest a basis to understand the pathobiology of CSC and possible strategies to attack them to undermine the self-renewal capacity of a tumor. [Cancer Res 2007;67(18):8425–8]