Abstract
Simple SummaryAlthough tyrosine kinase inhibitors (TKIs) are highly effective in the treatment of patients with chronic myelogenous leukemia (CML), leukemic stem cells (LSCs) are known to be resistant to TKIs. As a result, the application of immunotherapies against LSCs may cure CML.Introduction of tyrosine kinase inhibitors (TKIs) has improved the prognosis of patients with chronic myelogenous leukemia (CML), and treatment-free remission (TFR) is now a treatment goal. However, about half of the patients experience molecular relapse after cessation of TKIs, suggesting that leukemic stem cells (LSCs) are resistant to TKIs. Eradication of the remaining LSCs using immunotherapies including interferon-alpha, vaccinations, CAR-T cells, and other drugs would be a key strategy to achieve TFR.
Highlights
Chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm caused by t(9;22)(q34;q11) that produces the BCR-ABL1 fusion gene, which encodes protein with dysregulated tyrosine kinase activity
Recent analysis using next-generation sequencing has revealed that BCR-ABL1-dependent or-independent mutations exist in patients with poor response to tyrosine kinase inhibitors (TKIs) [106,107], suggesting that neoantigens other than known CML antigens could be targeted by immune checkpoint inhibitor (ICI)-activated cytotoxic lymphocytes (CTLs) which reside in these CML patients
Remaining CML-leukemic stem cells (LSCs) after TKI treatment are considered to be immunogenic, the immune system in CML patients is impaired at diagnosis, and restored by TKI
Summary
Chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm caused by t(9;22)(q34;q11) that produces the BCR-ABL1 fusion gene, which encodes protein with dysregulated tyrosine kinase activity. After cessation of TKI, about half of the patients could maintain a major molecular response (MMR) without TKIs, which is called treatment-free remission (TFR) [12,13,14]. In these patients, immune cells could have suppressed or eradicated persisting LSCs. We previously identified CXorf as an immunological target that is highly expressed in CML-LSCs. Antigen-specific cytotoxic lymphocytes (CTLs) were detected in the peripheral blood of patients who remained in molecular complete remission (CR). CML, chronic myeloid mic stem cells; TKI, tylosine kinase inhibitor; NK cells, natural killer cells; CTLs, cytotoxic T cells; IFN-α, interferon alpha
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