Fluorescence in situ hybridization: a sensitive method for trisomy 8 detection in bone marrow specimens

Area of Science:

• Hematology
• Cytogenetics
• Molecular Biology

Background:

• Trisomy 8 is a frequent chromosomal anomaly in bone marrow (BM) cells of patients diagnosed with myeloproliferative disorders (MPD), myelodysplastic syndromes (MDS), or acute nonlymphocytic leukemia (ANLL).
• Accurate detection of trisomy 8 is crucial for diagnosis and prognosis in these hematologic malignancies.

Purpose of the Study:

• To evaluate the efficacy of fluorescence in situ hybridization (FISH) for detecting trisomy 8 in BM specimens from patients with MPD, MDS, or ANLL.
• To assess the utility of FISH in identifying occult trisomy 8, particularly in cases with normal or equivocal conventional cytogenetic findings.

Main Methods:

• Analysis of interphase nuclei and metaphase spreads using FISH with chromosome 8-specific alpha-satellite and whole chromosome paint (WCP) DNA probes.
• Comparison of FISH results with conventional cytogenetic analysis in normal donors and patients with known trisomy 8.
• FISH analysis of BM from 144 patients with MPD, MDS, or ANLL and normal or abnormal karyotypes lacking trisomy 8.

Main Results:

• Normal BM samples showed minimal signals for trisomy 8 by FISH (≤2.0% interphase nuclei, ≤1 metaphase).
• FISH accurately identified trisomy 8 in 95-98% of specimens with confirmed trisomy 8 by conventional cytogenetics.
• FISH detected trisomy 8 in 7 patients with initially normal or uncertain conventional cytogenetic results, indicating its ability to identify occult cases.

Conclusions:

• Interphase and metaphase FISH are highly effective methods for detecting trisomy 8 in BM specimens.
• FISH analysis is particularly valuable for confirming or detecting trisomy 8 in patients with normal or uncertain conventional cytogenetic results.
• FISH offers a sensitive approach for diagnosing and monitoring hematologic malignancies associated with trisomy 8.