I realized in going over my reports that I never received the FISH report from my initial diagnosis. So I asked for it at the last Dr's appt. Since they initially suspected I had APML, they were looking for that in the FISH at first. The FISH results are somewhat confusing to me.
The FISH was done on PB. The report clearly states in what I surmise is a summary that 199/200 cells showed BCR-ABL, and that 9-22 translocation was detected by karyotype and FISH.
It then says the 15-17 translocation (for APML) was not detected by FISH.
I won't type in the CML part, since that is understandable. The weird part is related to the FISH for 15-17 translocation. Here is what it says:
Fluorescent in situ hybridisation (FISH) was undertaken on a smear of this sample, using a cocktail of probes for the t(15;17) (PML/RARA cytocell). Two hundred interphase nuclei were examined and 100/200 cells (50%) had an aberrant pattern of signals, with one RARA signal appearing to be half-size in about 50% of the cells and lost in the remaining cells. This result is outside the reference range for the probe (diploidy and no fusion signals in 98.81-100% cells) and suggested a translocation involving RARA with another chromosome. Following the identification of t(9;22) above, the experiment was repeated. While the same phenomenon was observed in a small number of the non-dividing nuclei, in the dividing (metaphase) cells, 20/20 metaphases examined had two equally sized RARA signals. This suggests that the previous result was due to technical artifact, and that there is no RARA deletion at this level of resolution.
Then it has the standard disclaimer "please remember that this analysis does not eliminate the possibility of alterations at the molecular level, chromosomal mosaicism involving abnormal cells lines of low frequency or small structural abnormalities".
Of course, I am most worried that the strange RARA results ARE due to some small abnormalities not picked up on the later tests, and that some day soon, my CML will transform into a rare APML blast crisis. (It does happen, but it's extremely rare.)
At the time I saw the doctor, I had not yet seen this FISH report, but I did press him on chromosome 17 abnormalities I was told about while in the hospital. (There also is a line in my karyotype report that says one cell (of 20) showed an additional loss of chromosomes, which he told me verbally at the hospital was chromosome 17. The report calls it technical artifact, and I know from my own research that loss of chromosomes is not considered clonal until at least 3 cells show it. But I've got no clue what causes a technical artifact for karyotyping.)
The doctor said the chromosome 17 abnormality on FISH indicated it was simply a bad test. They got bad results that weren't trustworthy. He said it was a bad probe or a bad test.
So, I am left wondering what "technical artifact" would cause a FISH signal for RARA (or any other chromosome) to be diminished? Bad probes? How is a probe "bad"? Is a blood smear more prone to error than other types of cell preps? (The FISH for t(9;22) does not mention a smear, only the t(15:17) says smear. I don't know how FISH samples are normally prepped for analysis. Are they all on smears?)
The first RARA test was run on interphase cells, on the same day as drawn. The second test was run the next day on the same sample, after they discovered the t(9;22). Would this affect the quality of the test, e.g., can I trust the 2nd test? It mentions that the same phenomenon was present in a small number of the non-dividing (interphase) cells, even though the metaphase cells appeared normal for RARA signals. What does this imply? That the probe didn't bind well to interphase cells? Are metaphase results always preferable to interphase results?
Any insight would be appreciated! Sorry if this is confusing, but I myself am confused.