"Although targeted drugs like Gleevec have revolutionized the treatment of chronic myelogenous leukemia CML patients generally must take them for the rest of their lives and may cease benefiting from them over time. In new research that could suggest a road to cure scientists at DanaFarber Cancer Institute and Boston Childrens Hospital have found that CML stem cells die in response to inhibition of a protein called Ezh. Drugs that target the protein are currently being tested in clinical trials for other cancers. The findings reported online today by the journal Cancer Discovery raise the prospect that Ezh blockers in combination with Gleevec and similar drugs could eradicate the disease in some patients in relatively rapid fashion or could be an effective therapy for those who become resistant to Gleeveclike agents the authors state. In a paper published simultaneously by Cancer Discovery a team of Scottish scientists report similar findings using a different research approach. The vast majority of patients with CML do remarkably well on imatinib Gleevec and similar drugs The disease is well controlled and side effects are tolerable says Stuart Orkin MD the studys senior author and a pediatric hematologistoncologist at DanaFarberBoston Childrens Cancer and Blood Disorders Center. In only  percent of patients however are the leukemia cells fully cleared from the body. The other  percent retain a reservoir of leukemic stem cells  which initiate the disease  and must stay on the drugs permanently. CML is a slowly progressing type of blood cancer that develops in the bone marrow. Primarily occurring in adults it is rare in children. Over time some patients develop resistance to Gleevec and other drugs that block BCRABL the misbegotten fusion protein that drives CML growth. Although second and thirdline targeted therapies can often return the disease to remission some patients dont benefit from these drugs or develop severe side effects. The new study grew out of efforts to discover whether different types of cancer are susceptible to Ezh inhibitors. In laboratory experiments the DanaFarberBoston Childrens researchers found not only that Ezh is overabundant in leukemia stem cells but that it helps them survive and give rise to fullfledged CML cells. Followup studies in mice showed that inactivating Ezh through geneediting techniques caused CML stem cells to die halting the disease at its source. The stem cells dependence on Ezh suggests they will be especially vulnerable to drugs that target the protein Orkin remarks. Such drugs are already in clinical trials for other diseases including lymphoma and some solid tumors.  Epizyme a biopharmaceutical company based in Cambridge MA recently opened a pediatric trial of an Ezh inhibitor for children with rhabdoid and other tumors. DanaFarberBoston Childrens is a site in the multicenter Phase  trial. Although adding Ezhtargeting 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 dont respond to Gleevec and similar drugs either initially or after drug resistance develops Orkin remarks. Our findings suggest inhibition of Ezh should be considered as a way to eradicate CML when used in combination with current targeted therapies. It offers a promising approach to shortening the duration of therapy in order to achieve a cure. If successful the cost savings of such an approach could also be significant. Joining senior author Orkin the studys lead author is Huafeng Xie PhD of DanaFarberBoston Childrens. Coauthors are Cong Peng Jialiang Huang PhD Bin E. Li PhD Woojin Kim Elenoe C. Smith Yuko Fujiwara PhD Partha P. Das Minh Nguyen of DanaFarberBoston Childrens Jun Qi PhD of DanaFarber James E. Bradner MD of DanaFarber and the Novartis Institute for BioMedical Research Shaoguang Li MD PhD of University of Massachusetts Medical School and Giulia Cheloni of UMass Medical School and the University of Florence Florence Italy. The study was funded in part by the National Institutes of Health grant UO CA and Hyundai Hope on Wheels. DanaFarberBoston Childrens Cancer and Blood Disorders Center  the nations top pediatric cancer center according to U.S. News  World Report  brings together two internationally known research and teaching institutions that have provided comprehensive care for pediatric oncology and hematology patients since . The Harvard Medical School affiliates share a clinical staff that delivers inpatient care at Boston Childrens Hospital and most outpatient care at DanaFarber Cancer Institute."