Cytogenetics Report

Today we got the cytogenetic information from Clara's leukemia cells. They were only able to grow 8 cells (this seems strange to me). On these 8 cells they performed GTW banding and FISH to identify abnormalities. From what I can tell they only used a few FISH probes instead of anti-chromosomal FISH that I've seen in seminars. I don't really follow much cytogenetic work so maybe they can accomplish the same thing with banding (So please make corrections all you genome biologists reading this). I have included a couple of pictures of the types of analysis below. Banding looks at the dark and light bands on the chromosomes based on chromatin density and FISH uses colored probes to identify specific stretches of DNA. In the example below each chromosome has its own color but in the analysis that was done on Clara's cells only specific (small) regions have probes. They were only looking for specific known rearrangements.

 

To help facilitate understanding of the changes in Clara, I will briefly go over chromosome structure (use figure below as a reference). Chromosomes have a center called the centromere which is where the two copies of the same chromosome come together prior to cell division. On each side of the centromere are the two arms of the chromosome. The shorter of the arms is called the p arm and the longer arm is called the q arm. These arms are segmented based on density of the DNA/protein (as observed through light/dark bands). The bands are labeled with the number increasing as one moves away from the centromere.

So her leukemia karyotype:

45, XX, -5, -7, add(10)(p), -11, add(11)(q23), +2mar[cp8]

What should it be? 46, XX

So what does all that mean? Her leukemia cells have 45 chromosomes (instead of 46). She is a normal XX (female). She is missing copies of 5, 7, and 11. **She has additional DNA on the p arm (the short arm) of chromosome 10 (I guess they don't know where). She also has additional DNA on part of the q arm of chromosome 11.** There are also two chromosomes that don't resemble known chromosomes (probably a mix of stuff) called marker chromosomes.

The FISH analysis indicated that there was a break at 11q23. This is a common break in leukemia in the middle of the MLL gene. They see that part of this gene (3' end) is with the additional DNA on chromosome 10 (add(10p)). This may indicate a translocation between chromosome 10 and 11 (t(10;11)) but I guess that they aren't sure or they would have labeled it so. t(10;11) translocations tend to happen in AML, but the exact location seems to matter. We know it is 11q23 somewhere in the MLL gene, but we don't know where on chromosome 10.** FISH also showed that EGR1 (a gene on chromosome 5 at a common break point) is normal and in two copies. This indicated that there isn't really a deletion of chromosome 5 but that it is probably part of the add() and/or marker chromosomes.

Missing chromosome 5 and 7 are usually linked with poorer prognosis potentially making her high risk. We have yet to hear from the doctors regarding her risk level and the last doctor seemed to indicate that she was standard risk. We will be talking to the AML expert to get a better explanation of these results in due time. If she is high risk then she is most likely going to need a bone marrow transplant.

EDIT: I made some changes between the **'s. I misunderstood what add() indicated and have corrected this.