Transformation Research

Nerd Alert.

I haven't written in a few days because I've been working my way through an article called "Characterization of a Case of Follicular Lymphoma Transformed into B-Lymphoblastic Leukemia," posted August 28 to the medical journal Molecular Cytogenetics. It's a genetics journal, and I'm no genetics expert, so I've been wading through it all weekend trying to wrap my head around it. I'm still  not sure I fully understand it, but I think I can at least tease out the important stuff.


I'm going to go ahead and assume that no one who is reading needs a full explanation of what Transformed Follicular Lymphoma is. Anyone interested in FL is probably really interested in its transformation.

So you probably know that Follicular Lymphoma most often transforms into Diffuse Large B-Cell Lymphoma, though it occasionally transforms in to other types as well. One of these less common types is B- Accute Lymphoblastic Leukemia (B-ALL), a very aggressive type of leukemia originating in the B-cells (immature B-cells multiply in the bone marrow and crowd out normal cells). It's a less common type of transformation, but apparently it does happen.

The geneticists who conducted this study were interested in this type of transformation on a molecular level. Basically, they found that the chromosome switch normally associated with Follicular Lymphoma (t(14;18)(q32;q21), also known as BCL2, or B-Cell Lymphoma #2, for all you genetics nerds) is followed by two other mutations, MYC (which messes with chromosome 8, related to the very aggressive Burkett's Lymphoma) and IGH (which messes with chromosome 14). Basically, while Follicular Lymphoma comes from a a screwed-up chromosome pair, B-Accute Lymphoblastic Leukemia comes from those chromosomes being messed up even more. Plus, there are a bunch of related genetic mutations involved in there, too. There's a heck of a lot going on. It's like a frickin' Marx Brothers movie in there.

I'm not sure that's really even the most important thing the researchers learned, especially given the relatively small number of Follicular Lymphoma patients who transform to B-ALL. They also make much of the method that they used to find these mutations. In short, they used a bunch of tools to look at the chromosomes from several angles: karyotype analysis (getting a picture of all of the chromosomes in a cell), fluorescence in situ hybridization (a cool technique that uses fluoresent probes that light up when certain chromosomes are present, helping to track their locations), microarray analysis and gene arrangement analysis. Each of these techniques tells a little bit different bstory about the chromosomes being studied. It seems like it's unusual that all of these are used at once, and the researchers seem to be making a case for what would otherwise seem like overkill in doing this kind of analysis.

The takeaway here would seem to be that, in a narrow sense, we may have a better way of identifying B-ALL on a chromosomal level. In a broader sense, we may have a better method for identifying lots of chromosomal mutations. In a still broader sense, we are another step closer to figuring out why transformation occurs, and maybe detecting it early.

What it doesn't mean is that we need to worry about transforming to B-ALL. It's still pretty rare. In fact, I'm not sure we need to worry about transforming at all.

Keep an eye out for it? Absolutely. Worry? No. We have lives to live.