Suzanne Turner on Cancer Stem Cells
The Alex Hulme Foundation was established in 2011 by Nicola and Dave Hulme in memory of their son Alex, who died of B-cell non-Hodgkin lymphoma (B-NHL) that year at age 12. Dedicated to furthering research and treatment of pediatric NHL, the foundation supports research on lymphomagenesis by Suzanne Turner, PhD, a research fellow and lecturer at the University of Cambridge, UK. Dr. Turner was awarded the prestigious Bennett Fellowship by Leukaemia & Lymphoma Research in 2007.
After learning how a personal flow cytometer could benefit her work, the foundation surprised Dr. Turner with a BD Accuri™ C6 flow cytometer at its annual Star Ball fundraiser last July. Dave Hulme described her reaction. “Thrilled is an understatement! Suzanne was surprised and shocked when we presented her with the instrument, as I had been apologizing to her that we hadn’t raised enough yet.”
Dr. Turner’s work for the foundation focuses on identifying cancer stem cells in B-NHL and characterizing their response to standard chemotherapy. She spoke to us about her research and why it’s crucial to have a flow cytometer at hand when rare tumor samples arrive at the lab.
Q: Would you tell us about the research program in which you are using the BD Accuri C6?
Dr. Turner: Our lab carries out research into the mechanisms and future treatment strategies for pediatric non-Hodgkin lymphoma (NHL). Broadly speaking, NHLs are classified as either B- or T-cell malignancies. Our research has focused on anaplastic large-cell lymphoma (ALCL), a T-cell lymphoma associated with a chromosomal translocation that aberrantly activates anaplastic lymphoma kinase (ALK). Much of our work has focused on understanding exactly what ALK does to initiate and maintain NHL.
More recently we have been examining intra-tumoral heterogeneity and how tumor cells interact with one another and with their microenvironment. These studies have shown that within the tumor, a small population of cells propagates tumor growth by not only producing the bulk of the tumor population, but also by providing soluble factors that support its growth. We refer to these cells as lymphoma stem or propagating cells.
It is these cells that we eventually need to target therapeutically. Whether they exist for all NHL remains to be investigated, so now our attention is turning to other forms of pediatric NHL, such as B-NHL.
Q: Could you describe a typical study using the BD Accuri C6?
Dr. Turner: When tumors come to the lab from the clinic, we first characterize them by using the BD Accuri C6 to assess their cell surface expression profile. As lymphoma derives from the hematopoietic system, we can use the well-defined CD marker expression system to classify the cells as resembling either a B- or T-cell lineage. We can then narrow down the cells' stage of lymphoid development using four-color stains with a variety of surface staining antibodies. One advantage of the BD Accuri C6 is that we can easily analyze how different tumor cell populations grow in vitro employing well-defined apoptosis, cell cycle, and proliferation assays.
So far we have been unable to discover a cell surface profile for the stem cells. We identify them using a side population technique on a cell sorter equipped with an ultraviolet laser.
Q: Would you describe your work with the Alex Hulme Foundation?
Dr. Turner: Pediatric lymphoma is often neglected due to its relative rarity in comparison to adult malignancies. However, it is a heterogeneous and complex disease that presents a very different set of problems from adults. Although cure rates are higher, children suffer most from the lifetime side effects of toxic chemotherapy and, as was the case with Alex, some still succumb to this disease.
Alex represents all those children we are failing to cure. With much-needed support from the Alex Hulme Foundation, we hope to find ways of increasing survival further whilst at the same time reducing side effects.
Q: What was your reaction when the Foundation presented you with a BD Accuri C6 for your work?
Dr. Turner: A BD Accuri C6 has long been on my "wish list" of lab equipment but had been financially out of reach for some time. We had an earlier model on trial when they were first on the market, and we did not want to give it back! But our research is completely funded by charities such as Leukaemia & Lymphoma Research in the UK. The cost of the BD Accuri C6, whilst comparatively low, was beyond the request limit for standard project grants.
When the Alex Hulme Foundation asked if there was any piece of equipment they could help us with, the BD Accuri C6 was the first thing to spring to mind. I did not expect them to be able to raise the funds in such a short time, and was astounded when they presented me with the cytometer at their Star Ball last July. I could not wait to get it back to the lab. [I picked it up on a Sunday and] by Monday morning we had it up and running. Setting up the instrument is simple and straightforward. It took us no more than an hour to put in place and calibrate, and it has been in constant use ever since.
Q: How has having a BD Accuri C6 in your lab changed your work?
Dr. Turner: In many cases, patient tumors (or murine tumors) arrive at our lab without prior warning, so we cannot always predict when we will need a flow cytometer. Flow cytometry facilities are generally booked days in advance, and the option of having a personal flow cytometer in the lab is invaluable to the progress of our work. Now, when tumors arrive, our first thought is not to contact all the flow cytometry facilities to find a slot, but rather to concentrate on the experiment in hand. The BD Accuri C6 has enabled us to make use of every single tumor that becomes available any time of the day or night. This is essential given the rarity of these specimens.
Ease of use is also important. Older, larger machines can be rather inhibitive to new, inexperienced staff members. With the BD Accuri C6, training is simple and quick. Users pick up the technique with relative ease and become independent in a short time.
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