UNM cancer researchers have discovered a genetic mutation underlying one of the most common childhood cancers, acute lymphoblastic leukemia.
Daily Lobo: Could you give me a brief overview of your findings?
Richard Harvey: Sure. The paper was in PNAS, which is Proceedings of the National Academy of Sciences, and it describes JAK mutations in leukemia. And JAK is a kinase, which is a protein involved in phosphoralating other proteins. Basically, it acts as a switch to turn on to modify other proteins to change their activity. So, what we had seen was a pattern of expression in leukemias that made us believe that there were kinases involved, but nobody had described any of the kinases. As part of this big project with Target, we identified a sequence mutation in these JAK correlated with very, very poor outcome, and (that) led us to the finding that we believe kinases will be involved in many more leukemias.
DL: What are the implications, then, of that correlation?
RH: The implications are that there are drugs out there to treat these kinases, so inhibitors of kinases and inhibitors of JAK, in particular, are currently on the market, so that's the difference. It's not a neat finding.but there are actually drugs in development and drugs on the market now which could be used to treat those diseases. So these are kids that don't respond to anything else. These kids have had normal therapy and, essentially, their survival after five years is approaching zero. They just do not respond to conventional therapy, so what we found is the thing that's unique to them, that had never been seen before, we believe is directly treatable with these kinase inhibitors.
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DL: What range of ages in children does this type of leukemia typically affect?
RH: Pretty much all kids. The range on the study we just did is probably from two to twenty-two, and the range.the disease affects all ages of kids. It's predominantly a childhood disease, so it really is a different disease than adults'.
DL: So this discovery helps to cure a specific kind of cancer. Can you envision a complete cure for cancer any time soon?
RH: The answer - as much as we'd love to believe differently - is 'No.' There will never be a single magic bullet. What this will do - the fact that kinases are involved in such a critical function and that they are targetable - makes us believe that this will apply to other cancers as well, so we could look for exactly the same types of things going on in solid tumors and we would expect that they would be treatable the same way. So, there won't be a single cure, but.when you identify these single genetic events that happen, then you can focus therapies on them rather than treat them generically... The drugs will be tailored to the specific events that are going on, not so generalized just to kill off all the cells.
DL: What's next in your research?
RH: More of these (types of experiments). We did 207 samples as part of this study, and out of those 207 samples there were about 10 percent that had this going on. We believe there are many, many more, who do extremely poorly, that have different types of things. So, we believe there will be other kinases that haven't been described yet that are likely to be involved in exactly the same development of the disease and, hopefully, are going to be treatable in exactly the same way. So, currently, we (are) examining the same set of patients looking for more of these type of things, and we're convinced they're there and working to increase the size of the study and look into other types of tumors as well.
