Dr. Naval Daver reviews the common mutations associated with acute myeloid leukemia (AML) and how the identification of these mutations affect prognosis.
Dr. Naval Daver is an Associate Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. More about Dr. Daver here.
What are common mutations in AML?
Yeah. So, the most common mutation in AML is F-L-T-3, FLT3 mutation. This is both prognostically important mutation, presence of an FLT3 in a newly diagnosed AML, has been shown in many large publications by the German Cooperative Group, British Cooperative Group, our group, and others, is associated with an inferior survival.
Also, now, on top of that, it is also a therapeutically important mutation in addition to having negative prognostic value because the addition of FLT3 inhibitors seems to dilute, to a large extent, the negative prognostic value.
So, we believe that if we can identify FLT3 mutations at FLT3 inhibitors, we can definitely improve the outcome of those patients.
The second most common is what we call NPM1 mutation, and that tends to occur with FLT3. About 55 percent of patients with an FLT3 mutation will have a coopering NPM1.
NPM1 is very interesting. With NPM1 mutation is present on it’s own without a FLT3, it’s actually associated with favorable outcome. It’s a favorable prognostic marker. However, if NPM1 is present with a FLT3, and especially if the FLT3 has a high quantity, high allelic load, then the NPM1 loses its favorable impact. So, now we’re kind of moving beyond just; do you have one mutation or not, which is what we thought 10 years ago, to; well, yes, you have this mutation, but what about the core-occurring mutation and even beyond. What about the burden, or what we call the variant allele frequency of that mutation?
So, for good or bad and I think it’s good in the end because it’s going to improve the patient outcomes, that we are getting more, more in-depth and there’s no longer quote, unquote, AML.
So, there’s a lot more granularity and analysis that is required even before starting treatment. And this is the thing that, in the community, we’re educating the doctors a lot, is that it’s okay to wait four to six days, especially if the patient does not have a very proliferative leukemia, to get the important bloodwork to identify the appropriate molecular and chromosome group.
So, that we can select the right treatment which will improve outcome rather than just rushing into standard treatment and missing a particular molecular chromosome group.