High incidence of minor and micro breakpoints in Chronic Myeloid Leukaemia with additional cytogenetic abnormalities at diagnosis – the Western Australian series

Abstract

Introduction and objective: Chronic Myeloid Leukaemia (CML) is defined by the presence of the Philadelphia chromosome, a balanced translocation between chromosomes 9 and 22 that results in the constitutively active tyrosine kinase, BCR-ABL1. Additional chromosomal abnormalities (ACAs) at diagnosis occur in 5–10% of CML patients, and are important for prognosis. They are classified as major or minor route. The purpose of our study was to determine the frequency and type of ACAs in 193 newly diagnosed CML patients, and to evaluate patient characteristics, treatment response, and survival. Methods: Medical records, in conjunction with data from the PathWest cytogenetics and molecular laboratories, were analysed. Results: ACAs were present in 14 (7.3%) of patients at diagnosis. Seven patients had major-route abnormalities, with additional chromosome 8 (+8) the most common. All patients were treated with tyrosine kinase inhibitors (TKIs). Three patients presented in blast crisis; two patients have died. Of note, there was a high incidence of the rare minor and micro BCR-ABL1 fusion transcripts. Conclusions: Frequency of ACAs at diagnosis was similar to that of previous reports. These patients consist a higher-risk cohort, and require individualised treatment, with consideration of frontline and secondary TKIs, adjunct chemotherapy, novel agents, and allogeneic stem cell transplant.

Keywords

• Chronic Myeloid Leukaemia
• Cytogenetics
• Leukaemia
• Tyrosine kinase inhibitors
• Additional chromosomal abnormalities