Nonclassical Philadelphia-positive FISH signal patterns in CML and seven cases with variant Philadelphia

Area of Science:

• Hematology
• Cytogenetics
• Molecular Biology

Background:

• Chronic Myeloid Leukemia (CML) is defined by the Philadelphia chromosome (Ph), resulting from t(9;22) translocation.
• Variant t(9;22) translocations occur in 5%-10% of CML cases, often with concurrent deletions in chromosomes 9 and 22.
• The prognostic impact of variant translocations and chromosomal deletions in CML remains unclear due to conflicting data and limited information on involved chromosomes.

Purpose of the Study:

• To investigate the clinical significance of nonclassical FISH signal patterns in CML.
• To determine the frequency of variant translocations in CML.
• To evaluate the association between classical and nonclassical FISH patterns and treatment response.

Main Methods:

• Analysis of bone marrow samples from 231 newly diagnosed CML patients.
• Utilized conventional cytogenetics and Fluorescence In Situ Hybridization (FISH) analysis.
• Compared treatment responses, survival times, and treatment changes between cases with classical and nonclassical FISH patterns.

Main Results:

• Nonclassical FISH signal patterns were observed in 49/231 cases.
• Variant t(9;22) was detected in seven cases, involving chromosomes 1, 3, 5, 7, 8, and 21.
• Cases with classical FISH patterns showed significantly higher treatment responses at the 6th month (p < 0.001) compared to nonclassical patterns.

Conclusions:

• Nonclassical FISH patterns, indicating deletions and/or variant translocations, may delay achieving a complete cytogenetic response.
• Larger case numbers are required to fully elucidate the prognostic implications of rare variant translocations.
• Clinical follow-up should consider that nonclassical FISH patterns might impact treatment response timelines in CML patients.