Battling Defiant Leukemia Cells

Released: 2-Oct-2013 12:00 PM EDT
Embargo expired: 7-Oct-2013 12:00 PM EDT
Source Newsroom: The Rockefeller University Press
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Citations Journal of Experimental Medicine

Newswise — Two gene alterations pair up to promote the growth of leukemia cells and their escape from anti-cancer drugs, according to a study in The Journal of Experimental Medicine.

Chronic myeloid leukemia (CML) is an aggressive cancer of the blood that is often treated with a drug called Imatinib (a.k.a. Gleevec). Although Gleevec is highly effective, some cancer cells can develop resistance to the drug. The mechanism that drives this resistance is not completely understood, but there is evidence that cancerous stem-like cells are particularly resistant and help to perpetuate disease.

CML stem-like cells rely on a protein called β -catenin for their survival and maintenance, and deletion of this protein in mice delays cancer growth. Another protein, IRF8, inhibits the survival of cells and is often reduced in CML cells, particularly in patients with advanced disease.

A group of scientists from the Max Delbrück Center for Molecular Medicine in Berlin now show that CML cells with activating β-catenin mutations are particularly resistant to Imatinib. Resistance is boosted further when this defect teams up with those that abolish IRF8 expression, rendering CML cells highly aggressive in mice. In fact, in CML cells lacking IRF8, β-catenin activation was essential for the cell's growth and survival.

Combined treatment with drugs that restore the expression of IRF8 and those that inactivate β-catenin may force these cells to surrender to treatment, preventing fatal leukemia progression.

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About The Journal of Experimental Medicine
The Journal of Experimental Medicine (JEM) is published by The Rockefeller University Press. All editorial decisions on manuscripts submitted are made by active scientists in conjunction with our in-house scientific editors. JEM content is posted to PubMed Central, where it is available to the public for free six months after publication. Authors retain copyright of their published works and third parties may reuse the content for non-commercial purposes under a creative commons license. For more information, please visit www.jem.org.

Scheller, M., et al. 2013. J. Exp. Med. doi: 10.1084/jem.20130706


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