Concomitant T315I and E459K mutations in chronic myeloid leukemia: A case report

The present report aims to improve the understanding of the clinicopathological features of chronic myeloid leukemia (CML) harboring concomitant T315I and E459K mutations. CML with the T315I mutation alone and in combination with other mutations has demonstrated sensitivity to olverembatinib, a third-generation tyrosine kinase inhibitor, providing valuable insights into potential treatment strategies for this rare mutational profile. In the present study, a 57-year-old woman with a 7-year history of CML relapsed 1 year after stopping imatinib treatment. The patient presented with right arm pain and bone lesions confirmed by imaging. Laboratory tests and bone marrow analysis confirmed CML in the chronic phase, and the patient initially responded well to dasatinib. After 5 months, severe pancytopenia developed. Next-generation sequencing (NGS) revealed concomitant T315I and E459K mutations in the breakpoint cluster region-Abelson tyrosine kinase 1 tyrosine kinase domain, as well as an ASXL transcriptional regulator 1 mutation, indicating progression to the blast phase. Treatment was switched to olverembatinib, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) was recommended. Overall, patients with multiple mutations in CML tend to have a worse prognosis due to treatment resistance and disease progression. NGS is crucial for detecting low-frequency mutations and allo-HSCT also serves a key role in treating high-risk cases.