LBRC outside projects
Non-invasive monitoring of drug effect on multiple myeloma cells
Recently, we embarked on new biological study on multiple myeloma with Kenneth Anderson Group in Dana-Farber Cancer Institute. Multiple myeloma (MM), a cancer of the plasma cell, is known to be the second most prevalent blood cancer. Although it is basically incurable, new promising drugs such as Bortezomib (PS-341) are being tested. According to phase II/III clinical trials, 46% of patients treated with the Bortezomib showed a response. In order to increase the response rate, however, and to prevent drug resistance for prolonged therapies, we need to investigate further the response of MM cells to the drugs.
Conventionally, the immunoblot and the fluorescent staining of proteasome-related proteins have been used to monitor the response of MM to drugs . The former is relatively cheap and fast while the latter is more quantitative. But, the immunoblot is basically an invasive technique, and the fluorescent staining has the problem of photo-bleaching which limits the duration of observation.
We note that tomographic phase microscopy (TPM) can be of useful tool since it is noninvasive and free from photo-bleaching. Its contrast, refractive index, is related to the concentration of proteins which is believed to be the indicator of drug response. Unlike normal plasma cells, the MM cells produce abnormal immunoglobulins, called M-proteins. In addition to this, the Bortezomib, the most promising drug for the MM, uses the protein-related pathway to induce the apoptosis of MM cells. Hence, the TPM armed with ability to quantify protein concentration can serve as a useful tool to monitor the drug response of MM cells.
- Bianchi G, Oliva L, Cascio P, et al. “The proteasome load versus capacity balance determines apoptotic sensitivity of multiple myeloma cells to proteasome inhibition,” Blood 113(13):3040–3049 (2009).