Acute lymphoblastic leukemia, or all, are the most common form of cancer in children. While the majority of children treated for this disease to survive in a subgroup of patients disease does not respond to treatment. Now, a team of scientists led by researchers at the Children Hospital Los Angeles and the University of California San Francisco (UCSF) have identified the reason for this resistance to drugs: BCL6, a protein that use Leukemic cells to stay alive despite chemotherapy. Targeting this protein provides a new mechanism of key to the fight against the drug resistant leukemia.
?We believe that this discovery is of immediate interest to the patient care,? said Markus M?schen, MD, a researcher at Hospital Los Angeles the Saban Research Institute of childhood and lead author of the study.
In a significant breakthrough, researchers working at children Hospital Los Angeles and UCSF have overcome resistance to drug therapy targeted, demonstrating the eradication of the disease of cancer cell and animal studies. The study, published in the May 19 of Nature, which shows an experimental drug, RI-BPI, developed at the Weill Cornell College of Medicine, used in combination with the drug Gleevec, closure stem cells that give rise to cells Leukemic cancer. Gleevec is a targeted and effective therapy against many different cancers, including of all, a cancer of white blood cells that affects older adults and young children. While Gleevec has greatly improved the survival of patients with leukemia, he continues to be a small subset of patients who do not respond to therapy and eventually die from their disease.
?Hopeless prognosis for a subset of all patients can radically change based on these results,? said co-author Ari Melnick, MD, Professor of Pharmacology at Weill Cornell Medical College, which initially developed RI-BPI. ?I am pleased to see that the BPI RI has such strong activity against leukemia?. This opens the possibility that the compound can have similar beneficial effects in other tumor types. ?
This new study shows that the BCL6 is active in all conduct by the Philadelphia (Ph + all) chromosome and that a combination of RI-BPI and Gleevec virtually ?extinguished? cancer. As described in the journal Nature this week, M?schen and his colleagues have shown that with mice of the drug resistant leukemia can be cured of the disease when given conventional anticancer drugs in combination with a compound that disables the BCL6 protein.
BCL6 protein was known of cancer researchers, because it is active in other forms of cancer. Reasoning that blocking BCL6 would Leukemic cells more sensitive to chemotherapy, scientists showed exactly that. Now, M?schen seeks ways to do the same with small molecules, which are generally easier to make a drug oral and cheaper to produce in mass than biotechnology drugs such as peptides. Last year, he received a grant of $ 3.6 million from the California Institute of regenerative medicine (CIRM) to develop such a molecule. Dr. M?schen is Associate Professor of Pediatrics, biochemistry and molecular biology at the Hospital Los Angeles research Children and Professor of medicine, laboratory at UCSF.
Article ?BCL6 allows Ph + cells in acute lymphoblastic leukemia survive inhibition of the kinase BCR-ABL1? was written by Cihangir Duy, Christian Hurtz, Seyedmehdi Shojaee, Leandro Cerchietti, Huimin Geng, Srividya Swaminathan, Lars Klemm, Soo ? mi Kweon, Rahul Nahar, Melanie BraigEugene Park, Kim Yong-miHofmann Wolf-Karsten, Sebastian Herzog, Hassan Jumaa, h. Phillip Koeffler, j. Jessica Yu, Nora Heisterkamp, Thomas g. Graeber, Hong Wu, b. Hilda Ye, Ari Melnick and Markus M?schen.
This work has been supported by grants from the National Institutes of Health and the National Cancer Institute, grants of leukemia and Lymphoma Society, the California Institute for regenerative medicine, William Laurence and Blanche Hughes Foundation and Stand up to Cancer-American Association for Cancer Research innovative research grant. Dr. M?schen and Dr. Melnick are specialists of the leukemia and Lymphoma Society.
Source:
Los Angeles children hospital
View the information on the drug Gleevec.
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