The methods of identification of cytogenetic changes that occur in various malignancies, the advantages and disadvantages of each methods and the implication of those cytogenetics with examples of acute leukemias (AML, ALL).
4. Fluorescence In Situ Hybridization
A molecular cytogenetic technique that uses
fl
uorescent probes to detect
speci
fi
c DNA sequences or entire chromosomes.
FISH can be used to identify a wide range of chromosomal abnormalities,
including deletions, duplications, and translocations
FISH
6. Advantages:
โข High sensitivity in detecting speci
fi
c abnormalities (high resolution).
โข Fast turnaround time.
โข Can be used on interphase nuclei.
Disadvantages:
โข Limited to known target abnormalities.
โข Requires speci
fi
c probes for each target.
โข Does not provide a comprehensive karyotye.
FISH
8. Advantages:
โข Provides a comprehensive analysis of the entire chromosome set.
โข Identi
fi
es novel and known abnormalities.
โข Allows the study of clonal evolution.
Disadvantages:
โข Requires cell culturing (metaphase) and specialized expertise.
โข Longer turnaround time.
โข Lower sensitivity for minor subclones (low resolution).
Karyotyping
12. t(15;17)
โข Characteristic feature of AML-M3 (acute promyelocytic leukemia)
โข Translocation of RARA on chromosome 17 to PML on 15.
โข This disrupts function of RARA (prevents maturation of promyelocytes)
โข Rx: ATRA & Arsenic trioxide.
โข Usually do not need treatment with intensive chemotherapy.
โข Lower risk of relapse
โข Speci
fi
c tool for MRD t(15;17) by RT-PCR.
Cytogenetics of AML
13. NPM1 & FLT3 mutation
โข Most common mutations in adult AML
โข NPM1 mutated AML are twice as likely to have FLT3 mutation
โข NPM1โ/FLT3โ โ Favourable prognosis (20%)
โข NPM1โ/FLT3โ โ Intermediate prognosis (15%)
โข NPM1โ/FLT3โ โ Unfavourable prognosis (6%)
โข Potential targets for emerging therapies.
โข NPM1 mutation is greatly stable with disease evolution, so it is a
potential target for MRD (minimal residual disease) detection.
Cytogenetics of AML
