A Case Series of Atypical BCR:: ABL1 Signal Patterns in Chronic Myeloid Leukaemia (CML) Patients

Abstract

Introduction: Chronic Myeloid Leukaemia (CML) is a myeloproliferative neoplasm defined by the BCR::ABL1 fusion gene resulting from the Philadelphia chromosome t(9;22)(q34.1;q11.2). Fluorescence in situ hybridization (FISH) is helpful in detecting both typical and atypical BCR::ABL1 rearrangement patterns. This case series highlights the clinical, cytogenetic and molecular implications of atypical signal patterns in CML patients. Methods: Four newly diagnosed CML patients exhibiting atypical BCR::ABL1 FISH signal patterns were included in this case series. Clinical features, cytogenetic findings, and molecular responses to frontline tyrosine kinase inhibitor (TKI) therapy were documented. Results: Each patient demonstrated distinct atypical signal patterns: Patient 1 had a deletion on derivative chromosome 9; Patients 2 and 3 showed deletions on derivative chromosome 22; Patient 4 exhibited BCR::ABL1 fusion with concurrent ABL1 and BCR deletions. Patients 1–3 failed to achieve major molecular remission during follow-up. Patient 4, although initially responsive, required a switch from imatinib to nilotinib due to loss of complete cytogenetic remission. Conclusion: Atypical BCR::ABL1 FISH signal patterns may correlate with suboptimal therapeutic responses to frontline TKIs. While their prognostic significance remains uncertain, these patterns offer valuable cytogenetic insights that may aid in early identification of patients at risk for treatment resistance or poor major cytogenetic response.