Chronic Myeloid Leukemia with S348L Mutation: A Case Report

Abstract

Background: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm driven by the BCR-ABL1 fusion gene, which leads to constitutive tyrosine kinase activity. Tyrosine kinase inhibitors (TKIs), such as imatinib, are the first-line therapy and have significantly improved patient outcomes. However, resistance can occur, often due to point mutations in the BCR-ABL1 kinase domain. The S348L mutation is a rare variant whose clinical significance remains unclear. While some mutations are associated with TKI resistance, the response to treatment may vary. This report presents a case of CML with a pre-treatment S348L mutation that showed an unexpectedly favorable response to imatinib, highlighting the importance of understanding the diverse clinical behavior of BCR-ABL1 mutations. Background: Chronic myeloid leukemia (CML) is driven by the BCR-ABL1 fusion gene and is primarily treated with tyrosine kinase inhibitors (TKIs). BCR-ABL1 kinase domain mutations may contribute to TKI resistance, but the clinical significance of rare variants such as S348L remains unclear. We report a CML case with a pre-treatment S348L mutation and a favorable response to imatinib. Case Presentation: A 47-year-old female presented with complaints of weakness and nausea for several days. Physical examination revealed pallor and splenomegaly. Laboratory tests showed anemia (Hb 7.6 g/dL), hyperleukocytosis (243.87 × 10³/μL), and thrombocytosis (1,168 × 10³/μL). Peripheral blood smear demonstrated a left shift with increased immature granulocytes, and bone marrow aspiration revealed hypercellularity, consistent with chronic phase chronic myeloid leukemia (CML). PCR-based sequencing of peripheral blood confirmed the S348L BCR-ABL1 kinase domain mutation before initiating therapy. The patient was treated with first-line imatinib (400 mg daily). After one year of treatment, she achieved a major molecular response (MR4.5), with a BCR-ABL1 transcript level of 0.0021% (International Scale), indicating an excellent therapeutic response despite the pre-existing mutation. Conclusion: Despite the pre-treatment S348L mutation, the patient achieved a deep molecular response to first-line imatinib. This case suggests that S348L does not invariably confer imatinib resistance and highlights the variable clinical significance of rare BCR-ABL1 mutations. Further studies are warranted to clarify their prognostic and therapeutic implications.