Abstract
Stem cells are an integral component of normal mammalian physiology and have been intensively studied in many systems. Intriguingly, substantial evidence indicates that stem cells also play an important role in the initiation and pathogenesis of at least some cancers. In particular, myeloid leukemias have been extensively characterized with regard to stem and progenitor cell involvement. Thus, as a focal point for both scientific and therapeutic endeavors, leukemic stem cells (LSC) represent a critical area of investigation. LSC appear to retain many characteristics of normal hematopoietic stem cells (HSC) as evidenced by a hierarchical developmental pattern, a mostly quiescent cell cycle profile, and an immunophenotype very similar to HSC. Consequently, defining unique properties of LSC remains a high priority in order to elucidate the molecular mechanisms driving stem cell transformation, and for developing therapeutic strategies that specifically target the LSC population. In this review, we discuss emerging concepts in the field and describe how various molecular and cellular characteristics of leukemia cells might be exploited as a means to preferentially ablate malignant stem cells.
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Acknowledgements
We gratefully acknowledge the assistance from Drs Mahesh Vaisnav and Fay Young in critical evaluation of this manuscript. The study was supported by grants from the NIH (R01-CA90446) and the American Cancer Society (RSG-03-096-01-LIB). CTJ is a scholar of the Leukemia and Lymphoma Society.
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Jordan, C., Guzman, M. Mechanisms controlling pathogenesis and survival of leukemic stem cells. Oncogene 23, 7178–7187 (2004). https://doi.org/10.1038/sj.onc.1207935
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DOI: https://doi.org/10.1038/sj.onc.1207935
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