Project Term
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Project Summary
Most of the Hairy Cell Leukemia variant patients do not respond to conventional therapies. They develop resistance to the chemotherapy drugs and we will investigate why this happens. Our data shows that a protein called BAFF is playing a key role in providing additional survival advantages to these patient cells to resist therapies. We will develop new treatment methods by targeting this protein in order to make these patients sensitive to therapy and to improve clinical outcome.
Lay Abstract
Hairy Cell Leukemia variant (HCLv) patients achieve only a partial response to standard therapies which factors into their decreased median overall survival rate of 9 years. Some patients have demonstrated success with splenectomy, splenic irradiation and immunotherapy. To improve outcomes for HCLv patients, it is necessary to identify the factors providing survival signals to these cancer cells. There are many factors produced by tumor cells and cells near the tumor which favors tumor growth and help them to resist treatments. We found that blood of HCLv patients has a high amount of a protein named B-cell activating factor (BAFF). This protein BAFF has to bind to certain other proteins called “receptors” on the surface of cells to exert an effect on those cells. So, we checked whether HCLv cancer cells has receptors of BAFF and indeed they showed expression of all three receptors of BAFF protein. That means BAFF can bind to these cancer cells and make a functional impact on them. Interestingly, our data shows that BAFF is giving extra survival signals to these HCLv cancer cells so that they are protected from chemotherapy. In this grant proposal, (1) we want to inhibit this protein BAFF and its receptors and see if these cancer cells are becoming more vulnerable to chemotherapy. We will use our newly developed mouse models to test these combination therapies. We anticipate these new therapies will improve HCLv patients treatment outcome and survival.
The Hairy Cell Leukemia Foundation (HCLF) and Blood Cancer United have joined forces to create the Hairy Cell Leukemia Research Initiative program to support targeted research to build a more comprehensive foundational understanding of the molecular basis of hairy cell leukemia (HCL), develop additional therapies, and optimize outcomes for patients with this disease.
Program
