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Each year in the United States, approximately 5,000 people are diagnosed with CML. Most cases of CML are characterized by a chromosomal abnormality—the Philadelphia chromosome—in which genetic material is exchanged between chromosome 9 and chromosome 22. This exchange brings together two genes: BCRand ABL. The combination of these two genes into the single BCR-ABL gene results in the production of a protein that contributes to uncontrolled cell growth.

Recognition of the pivotal role of the BCR-ABL protein in CML led to the development of Gleevec & Tasigna, 2 tyrosine kinase inhibitor (TKI) drugs which block the activity of this protein. TKI’s produce high rates of remission among patients with chronic-phase CML, dramatically changing the treatment of this disease. However, patients must take them for the rest of their lives and the CML often develops resistance.

Doctors have now discovered that CML stem cells die in response to inhibition of a protein called Ezh2. Drugs that block Ezh2 may represent a new treatment option and when combined with a TKI might eradicate the CML in some patients.

Although adding Ezh2-targeting agents to the standard drug regimen for CML has the potential to dramatically shorten the treatment period for many patients, ethical considerations may lead to the agents’ first being tested in patients who don’t respond to a TKI, either initially or after drug resistance develops.

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Epizyme, a biopharmaceutical company based in Cambridge, MA, has recently opened a pediatric trial of an Ezh2 inhibitor in children.


Epizyme Expands Clinical Programs through Cooperative Research and Development Agreements with the National Cancer Institute. [Press release.] Can be accessed at

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