2. Fluorescent In-situ Hybridization (FISH) Studies
• D-FISH (double-FISH) reduces the rates of false positivity.
• Interphase FISH does not require cells to be dividing and thus can represent a wider
population of cells. Interphase FISH is commonly used.
• FISH studies are generally done from peripheral blood and analyzes approximately 200
interphase cells and is so more sensitive than CA.
• There is also a narrower confidence level. For a patient having 50/200 positive CML cells
or 25%Ph+, the 95% confidence interval is 19-32%.
Disadvantages:
• Most FISH laboratories have an upper limit of false positivity of 1-5%. This is a limitation
of the technique.
• Long-term studies have not been done to see the relationship between cytogenetic response
as measured by FISH and survival.
• Due to the false positivity rate, care has to be maintained by clinicians to deem failure of
treatment based on low FISH levels.
Advantages:
• FISH at diagnosis can detect Ph negative BCR-ABL positive CML. In this kind of disease,
the Ph chromosome may be masked and not detected by a BMA cytogenetic analysis. However,
FISH or PCR can be used to detect the BCR-ABL gene or transcript.
• FISH is a useful tool to detect the deletion of chromosome 9, which in the Interferon era
was associated with a worse disease prognosis but may not be so in the Gleevec era.
• FISH at diagnosis is useful as a pretreatment baseline if further monitoring by FISH is used
to measure the leukemic burden.
• In the case of myelosuppression (low counts), a BMA cytogenetics may be difficult to do,
FISH from peripheral blood can serve as an useful guide to the leukemic burden.
Recommendations by CML experts is to routinely check by peripheral blood FISH until 10%Ph+
is reached when a CCR can be confirmed by CA.