Somatic mutations may predict treatment failure with tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukemia (CML), according to a study published in Blood, the journal of the American Society of Hematology.
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While TKIs have demonstrated remarkable success at improving the life expectancy of patients with CML, some patients develop a resistance to this class of drugs over time. Why this occurs in some patients and not others is not yet fully understood. Somatic mutations, commonly detected in a variety of myeloid neoplasms have not yet been systematically investigated.
Therefore, in a study led by TaeHyung Kim, University of Toronto, Canada, researchers evaluated how preleukemic somatic mutations affected TKI effectiveness in patients with CML.
For the study, they performed deep sequencing on 300 serial samples from 100 patients with CML. A total of 37 patients carried mutations, 16 of which originated from preleukemic clones.
After patients were treated with TKIs, researchers identified 5 distinct mutation patterns, the most significant of which was Pattern 2. In this pattern, the acquisition of new mutations during therapy resulted in TKI treatment failure. They also found that mutation burden often persisted despite successful TKI response (Pattern 1), providing indirect evidence that these mutations also originated from preleukemic mutations, while patients exhibiting mutation clearance (Pattern 3) showed mixed clinical outcomes.
“These patterns show that CML mutation dynamics following TKI therapy are markedly distinct from other myeloid neoplasms,” authors of the study wrote.
They concluded that while mutation patterns can differ significantly among patients, correlations could be drawn between CML mutation patterns and treatment success with TKIs. More research is needed analyzing how different mutations function when treated with these and other drug types so that clinicians can better care for patients with all forms of CML.
