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

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dc.contributor.authorMisaghian, Neginen_US
dc.contributor.authorLigresti, Giovannien_US
dc.contributor.authorSteelman, L. S.en_US
dc.contributor.authorBertrand, Fred E.en_US
dc.contributor.authorBasecke, Jorgen_US
dc.contributor.authorLibra, Massimoen_US
dc.contributor.authorNicoletti, Ferdinandoen_US
dc.contributor.authorStivala, F.en_US
dc.contributor.authorMilella, Micheleen_US
dc.contributor.authorTafuri, A.en_US
dc.contributor.authorCervello, Melchiorreen_US
dc.contributor.authorMartelli, Alberto M.en_US
dc.contributor.authorMcCubrey, James A.en_US
dc.date.accessioned2011-01-21T19:19:56Zen_US
dc.date.accessioned2011-05-17T01:39:58Z
dc.date.available2011-01-21T19:19:56Zen_US
dc.date.available2011-05-17T01:39:58Z
dc.date.issued2009-01en_US
dc.description.abstractSince 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 รข 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 2009en_US
dc.identifier.citationLeukemia; 23:1 p. 25-42en_US
dc.identifier.pmidPMC2627788en_US
dc.identifier.urihttp://hdl.handle.net/10342/3058en_US
dc.language.isoen_USen_US
dc.publisherEast Carolina Universityen_US
dc.relation.urihttp://www.nature.com/leu/journal/v23/n1/full/leu2008246a.htmlen_US
dc.subjectDrug transportersen_US
dc.subjectDrug resistanceen_US
dc.subjectTumor-initiating cellen_US
dc.subjectStem Cellsen_US
dc.subjectTargeted therapyen_US
dc.titleTargeting the leukemic stem cell: the Holy Grail of leukemia therapyen_US
dc.typeArticleen_US

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