Chronic myeloid leukemia and NK cell immunity

BCR-ABL1 tyrosine kinase inhibitors (TKIs) have dramatically improved the long-term outcomes of patients with chronic myelogenous leukemia (CML). Notably, approximately half of patients with a sustained deep molecular response experienced treatment free remission (TFR) even after discontinuation of TKI. Although antitumor immunity by natural killer (NK) cells might contribute to the effects of TKI and TFR in CML, the details of their actions have not as yet been elucidated. Recently, several reports have raised the possibility that the killer immunoglobulin-like receptor (KIR), a highly polymorphic NK cell receptor, may play important roles, because polymorphic patterns of KIR were shown to be associated with the intensity of clinical responses and outcomes in TKI-treated CML patients. Herein, we summarize genetic and immunological aspects of KIR, and also discuss the association between KIR and CML. If KIR polymorphism is actually associated with the outcomes of TKI-treated CML patients, we might be able to obtain prognostic information for patients and assess the possibility of TFR, which would not only benefit patients, but also provide a platform for improving the outcomes of other hematologic malignancies utilizing NK cell immunity.