Getting to Know the Molecular Landscape of R/R Chronic Myeloid Leukemia: NGS-Based Profiling of Myeloid Mutations Beyond BCR/ABL

Introduction: Even in the tyrosine kinase inhibitors (TKIs) era, there's still a subgroup of patients with chronic myeloid leukemia (CML) with poor response to treatment and therefore worse prognosis. The most frequent cause of resistance to treatment is the mutation in ABL fusion protein reported in 15-25% of the failures to TKIs. Nevertheless, there are other several factors not clearly described yet in published data, including myeloid mutations assessed by Next-Generation Sequence (NGS) beyond BCR-ABL kinase domain mutations. Methods: We performed a multicenter, open, prospective trial to identify the frequency and clinical implications of myeloid mutations. We included all patients with relapsed/refractory CML to any TKI defined as failure to achieve cytogenetic response at 3 months or decrease