Abstract
The magnitude of the natural killer (NK) cell response contributes to the achievement of treatment-free remission (TFR) in patients with chronic myeloid leukemia (CML) and is regulated by the interaction between killer immunoglobulin-like receptors (KIRs) on NK cells and human leukocyte antigen (HLA) class I molecules on target cells. The abundant combination between KIR and HLA through genetic polymorphisms determines the functional diversity of NK cells. We previously reported that KIR3DL1-HLA-Bw status is associated with achievement of TFR by reflecting NK cell potential. Patients with strong interaction between KIR3DL1/HLA-Bw were identified as having a higher molecular relapse risk, based on the "missing self" hypothesis which suggests that the lack of cognate ligands for KIRs may induce target cell lysis. However, all the patients with strong interaction between KIR3DL1/HLA-Bw who received prior IFN-α therapy achieved TFR (p = 0.007), explained by the "NK cell licensing" concept, whereby NK cells become more functional through the recognition "self" HLA class I molecules by KIRs. NK cell licensing may contribute to the potential efficacy of IFN-α treatment in patients with CML. We defined high-risk molecular relapse patients and suggest that KIR3DL1/HLA-Bw status may help detect patients who could benefit from IFN-α for maintaining TFR.