Spectrum of somatic mutation dynamics in chronic myeloid leukemia following tyrosine kinase inhibitor therapy. Homo sapiens

Somatic mutations commonly detected in a variety of myeloid neoplasms have not been systematically investigated in chronic myeloid leukemia (CML). We performed targeted deep sequencing on a total of 300 serial samples from 100 CML patients; thirty-seven patients carried mutations. Ten of these carried mutations originating from clonal hematopoiesis. Using unsupervised hierarchical clustering, we identified five distinct patterns of mutation dynamics arising following tyrosine kinase inhibitor (TKI) therapy. This study demonstrates that patterns of mutation acquisition, persistence, and clearance vary but have a number of interesting correlations with clinical outcomes. Mutation burden often persists despite successful TKI response (Pattern 1), while patients exhibiting mutation clearance (Pattern 3) show mixed clinical outcomes. Unsurprisingly, patients acquiring new mutations during treatment failed TKI therapy (Pattern 2). These patterns show that CML mutation dynamics following TKI therapy are markedly distinct from other myeloid neoplasms. In summary, clinical implications of mutation profiles and dynamics in CML should be interpreted with caution.