Targeting the leukemic stem cell: the Holy Grail of leukemia therapy
Misaghian, N; Ligresti, G; Steelman, LS; Bertrand, Fred E.; Basecke, Jorg; Libra, M; Nicoletti, F; Stivala, F; Milella, M; Tafuri, A; Cervello, M; Martelli, AM; McCubrey, JA
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 chemo-therapeutic drugs and the involvement of growthpromoting 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 smallmolecule 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 â 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. Originally published Leukemia, Vol. 23, No. 1, Jan 2009
Misaghian, N, & Ligresti, G, & Steelman, LS, & Bertrand, Fred E., & Basecke, Jorg, & Libra, M, & Nicoletti, F, & Stivala, F, & Milella, M, & Tafuri, A, & Cervello, M, & Martelli, AM, & McCubrey, JA. (January 2009). Targeting the leukemic stem cell: the Holy Grail of leukemia therapy. Leukemia, 23(1), 25- 42. Retrieved from http://hdl.handle.net/10342/3058
Misaghian, N, and Ligresti, G, and Steelman, LS, and Bertrand, Fred E., and Basecke, Jorg, and Libra, M, and Nicoletti, F, and Stivala, F, and Milella, M, and Tafuri, A, and Cervello, M, and Martelli, AM, and McCubrey, JA. "Targeting the leukemic stem cell: the Holy Grail of leukemia therapy". Leukemia. 23:1. (25-42), January 2009. September 21, 2018. http://hdl.handle.net/10342/3058.
Misaghian, N and Ligresti, G and Steelman, LS and Bertrand, Fred E. and Basecke, Jorg and Libra, M and Nicoletti, F and Stivala, F and Milella, M and Tafuri, A and Cervello, M and Martelli, AM and McCubrey, JA, "Targeting the leukemic stem cell: the Holy Grail of leukemia therapy," Leukemia 23, no. 1 (January 2009), http://hdl.handle.net/10342/3058 (accessed September 21, 2018).
Misaghian, N, Ligresti, G, Steelman, LS, Bertrand, Fred E., Basecke, Jorg, Libra, M, Nicoletti, F, Stivala, F, Milella, M, Tafuri, A, Cervello, M, Martelli, AM, McCubrey, JA. Targeting the leukemic stem cell: the Holy Grail of leukemia therapy. Leukemia. January 2009; 23(1): 25-42. http://hdl.handle.net/10342/3058. Accessed September 21, 2018.
East Carolina University