Clinical features and treatment response to TKIs in chronic myeloid leukemia patients with atypical BCR::ABL1 transcripts

A small percentage (0.3 %-4.6 %) of chronic myeloid leukemia (CML) patients exhibit atypical transcripts with poorly defined clinical implications. To explore the clinical features and treatment response in those patients, this study retrospectively analyzed 52 CML patients with eight types of atypical transcripts. The three most common types were e19a2, e1a2, and e13a3/e14a3. Compared to patients with typical transcripts, those with e19a2 (n = 17) were older, more frequently female, and had elevated platelet levels. Similarly, patients with e1a2 (n = 6) were predominantly female. Regarding treatment response, the lower cumulative rates of complete cytogenetic response (CCyR) by 1 year were seen in patients with e19a2 (41.2 % vs 85.3 %) and e1a2 (16.7 % vs 87.5 %). The probabilities of failure-free survival (FFS) were lower in patients with e19a2 and e1a2. Additionally, the probabilities of progression-free survival (PFS) were lower in patients with e19a2. However, overall survival (OS) was comparable between atypical and typical cohorts, likely attributable to salvage therapy with second-generation TKIs. No differences were found in clinical features, treatment response, and outcomes among patients with e13a3/e14a3 (n = 11). Notably, rare subtypes exhibited diverse disease manifestations, with e8a2 (n = 3) linked to indolent course and e6a2 (n = 2) associated with rapid progression. In general, atypical transcript subtypes define a clinically heterogeneous CML subgroup with differential TKI sensitivity. Patients with e19a2 and e1a2 transcripts exhibit potential resistance to imatinib but achieve similar outcomes to patients with typical transcripts under second-generation TKI therapy.