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- Title
Targeting the leukemic stem cell: the Holy Grail of leukemia therapy.
- Authors
Misaghian, N; Ligresti, G; Steelman, L S; Bertrand, F E; Bäsecke, J; Libra, M; Nicoletti, F; Stivala, F; Milella, M; Tafuri, A; Cervello, M; Martelli, A M; McCubrey, J A; Bäsecke, J
- Abstract
Since the discovery of leukemic stem cells (LSCs) over a decade ago, many of their critical biological properties have been elucidated, including their distinct replicative properties, cell surface phenotypes, their increased resistance to chemotherapeutic drugs and the involvement of growth-promoting chromosomal translocations. Of particular importance is their ability to transfer malignancy to non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice. Furthermore, numerous studies demonstrate that acute myeloid leukemia arises from mutations at the level of stem cell, and chronic myeloid leukemia is also a stem cell disease. In this review, we will evaluate the main characteristics of LSCs elucidated in several well-documented leukemias. In addition, we will discuss points of therapeutic intervention. Promising therapeutic approaches include the targeting of key signal transduction pathways (for example, PI3K, Rac and Wnt) with small-molecule inhibitors and specific cell surface molecules (for example, CD33, CD44 and CD123), with effective cytotoxic antibodies. Also, statins, which are already widely therapeutically used for a variety of diseases, show potential in targeting LSCs. In addition, drugs that inhibit ATP-binding cassette transporter proteins are being extensively studied, as they are important in drug resistance-a frequent characteristic of LSCs. Although the specific targeting of LSCs is a relatively new field, it is a highly promising battleground that may reveal the Holy Grail of cancer therapy.
- Subjects
LEUKEMIA treatment; STEM cells; CELL membranes; CHROMOSOMAL translocation; CANCER treatment; CANCER chemotherapy; DRUG delivery systems; LEUKEMIA; TREATMENT effectiveness
- Publication
Leukemia (08876924), 2009, Vol 23, Issue 1, p25
- ISSN
0887-6924
- Publication type
journal article
- DOI
10.1038/leu.2008.246