What factors help determine if MDS will transform into AML?

I think that sequencing can help sort of give you a prediction of whether or not might go from MDS to AML. There's some mutations that are pretty well associated. One would be a mutation in this gene called p53, which is the most frequently mutated gene in all cancers. So, that can help you.

I think that the one thing to remember is that even if you have these prognostic factors, it might be you're in the scoring system, it might be a specific blast count, it might be that you have specific mutations. All of those provide a risk. So there are very few of them that say you had this, so you're going to get to AML. It's always a chance. Is it a higher or lower chance that you're going to get there? Right. But almost none are 100% saying, yes, you're going to get it or no, you're never going to get it.

So these are all sort of risk things. So when people say why have like these mutations, it doesn't necessarily mean that you're going to get there. It just means we have to have more vigilance about making sure that we know if you're going in there. Because we might want to start treating you earlier rather than waiting till you have full blown AML.

Are there certain types of MDS that are more likely to progress into AML?

That's the million dollar question. So my lab has been interested in that. Many other labs in the world have been interested in that. The one thing about MDS, it is a syndrome, the S is syndrome. So what that means is that it is actually a collection of probably 100 different diseases, each one having different mutations and so, if you have like this conglomeration of a bunch of diseases, they just all kind of look the same.

It's sort of like if you have pneumonia, you can have pneumonia from bacteria, you could have pneumonia from a virus, you could have, but they're all pneumonia. So myelodysplastic syndrome, you could have MDS give you a bunch of different variants. And so when you think about that, it becomes very complex. And so we're all trying to find ways of defining it more precisely.

And then in each one of those cases, it's probably maybe a different trigger that turns it into AML. So just as a whole, nobody knows for very specific things we're starting to understand. Higher risk MDS, which is based off of the bone marrow biopsy results and the blood count's mutational profile and the chromosomes that can be seen under the microscope. Those patients with high risk MDS have a higher risk of progressing to AML.

Right now, we have individualized scoring systems which can let us know and try and predict with greater accuracy how likely one is to progress to AML with a higher risk MDS. It varies based off of a bunch of different factors.