2012 Research Grants
Targeting BCL6 in Acute Myeloid Leukemia (AML) Stem Cells.
Conducted by Dr. Cihangir Duy at the Weill Cornell Medical College. Funded in Partnership with the Leukemia & Lymphoma Society.
While conventional chemotherapy kills fast-growing AML cells, it often fails to destroy a group of stem cells and other "survivor" cells. As a result, the patient may seem to be responding but the cancer inevitably returns. The survivor cells are able to outwit existing treatments through a process in which they go dormant and therefore "under the radar" of chemotherapy, then resume activity once the threat is gone.
Dr. Duy is taking a three-pronged aproach to target stem and other survivor cells. He has found that cells under stress reprogram their cellular functions through specific “epigenetic” changes (that is, changes that alter the instructions the genes would otherwise provide.) He also found a protein called “ATR” to be a main player in the cell’s stress response. By targeting two key epigenetic regulators, Dr. Duy has been able to successfully re-sensitize some drug-resistant survivor cells to chemotherapy. In addition, by inhibiting ATR in combination with chemotherapy, he has been able to compromise AML cell ”dormancy”, resulting in death of all survivor cells. His upcoming work will address the third prong of attack, determining how the protein BCL6 protects cancer cells and whether the inhibitor RI-BPI will disrupt this function.
The project will be conducted by Dr. Cihangir Duy, above, whose research has revealed surprising new roles for the BCL6 oncogenic transcriptional repressor in the development and progression of leukemia.