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.

Targeting the leukemic stem cell: the Holy Grail of leukemia therapy / N., Misaghian; G., Ligresti; L. S., Steelman; F. E., Bertrand; J., Basecke; M., Libra; F., Nicoletti; F., Stivala; M., Milella; Tafuri, Agostino; M., Cervello; A. M., Martelli; J. A., Mccubrey. - In: LEUKEMIA. - ISSN 0887-6924. - 23:1(2009), pp. 25-42. [10.1038/leu.2008.246]

Targeting the leukemic stem cell: the Holy Grail of leukemia therapy

TAFURI, Agostino;
2009

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.
2009
drug resistance; drug transporters; stem cells; targeted therapy; tumor-initiating cell
01 Pubblicazione su rivista::01a Articolo in rivista
Targeting the leukemic stem cell: the Holy Grail of leukemia therapy / N., Misaghian; G., Ligresti; L. S., Steelman; F. E., Bertrand; J., Basecke; M., Libra; F., Nicoletti; F., Stivala; M., Milella; Tafuri, Agostino; M., Cervello; A. M., Martelli; J. A., Mccubrey. - In: LEUKEMIA. - ISSN 0887-6924. - 23:1(2009), pp. 25-42. [10.1038/leu.2008.246]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/229049
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