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

TL;DR

This study examines nonclassical FISH signal patterns and variant translocations in CML patients, finding that classical patterns correlate with better early treatment responses.

Contribution

The study identifies nonclassical FISH patterns and variant translocations in CML and links classical patterns to improved early treatment outcomes.

Findings

Nonclassical FISH signal patterns were detected in 49 out of 231 CML cases.

Seven cases of variant t(9;22) were identified, involving chromosomes 1, 3, 5, 7, 8, and 21.

Classical FISH signal patterns correlated with significantly higher treatment responses at the 6th month (p < 0.001).

Abstract

Chronic myeloid leukemia (CML) is characterized by the Philadelphia chromosome (Ph), which occurs as a result of t(9;22). In 5%–10% of CML cases, variant t(9;22)s are observed. Additionally, while t(9;22) is formed, deletions can be observed in chromosomes 9 and 22. These deletions are observed more frequently in variant t(9;22). There is conflicting information in the literature about the prognostic effects of variant t(9;22) and deletions of 9q and 22q. There is also limited information about the frequency and breakpoints of other chromosomes involved in the variant t(9;22). Signal patterns other than the classical signal pattern of FISH analysis indicate deletions and variant translocations. In this study, we aimed to investigate the clinical significance of nonclassical FISH signal patterns and to determine the frequency of variant translocations.

Bone marrow samples from 231 newly diagnosed CML patients were analyzed by conventional cytogenetics and FISH.

As a result of FISH analysis, nonclassical FISH signal patterns were detected in 49/231 cases, and variant t(9;22) was detected in seven cases by conventional cytogenetics. It was determined that chromosomes 1, 3, 5, 7, 8, and 21 were involved in variant t(9;22). When cases with classical and nonclassical signal patterns were compared in terms of 6th- and 12th-month treatment responses, survival times, and treatment changes, it was found that cases with classical signal patterns had significantly higher treatment responses at the 6th month (p < 0.001).

Because variant translocations are extremely rare and involve many different chromosomal breaks, a large number of cases are needed to clearly understand their prognostic implications. Due to the limitations of conventional cytogenetic analyses, it should be considered in patient follow-up that nonclassical FISH signal patterns indicating deletions and/or variant translocations may cause a delay in obtaining a complete cytogenetic response at the 6th month.

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