KIR-Genetic Factors and Response to Tyrosine Kinase Inhibitor Therapy in Chronic Myeloid Leukemia

AUTOIMMUNE THROMBOCYTOPENIA

EV Kuzmich1, IE Pavlova1, LN Bubnova1,2, SS Bessmeltsev1

1 Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya ul., Saint Petersburg, Russian Federation, 191024

2 IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo ul., Saint Petersburg, Russian Federation, 197022

For correspondence: Elena Vital’evna Kuzmich, PhD in Biology, 16 2-ya Sovetskaya ul., Saint Petersburg, Russian Federation, 191024; Tel.: +7(921)912-52-07; e-mail: yelenakuzmich@gmail.com

For citation: Kuzmich EV, Pavlova IE, Bubnova LN, Bessmeltsev SS. KIR-Genetic Factors and Response to Tyrosine Kinase Inhibitor Therapy in Chronic Myeloid Leukemia. Clinical oncohematology. 2023;16(2):119–27. (In Russ).

DOI: 10.21320/2500-2139-2023-16-2-119-127

ABSTRACT

The development of tyrosine kinase inhibitors (TKIs) and their introduction into clinical practice considerably improved the prognosis for chronic myeloid leukemia (CML) patients. About 50 % of patients with achieved deep molecular response are eligible for safe TKI discontinuation. Despite these advances, no reliable biomarkers are known to predict a response and sustaining treatment-free remission after TKI withdrawal. As TKIs do not destroy leukemic stem cells, which can be responsible for relapse, critical importance in CML is attached to natural killers (NK-cells) having antitumor activity. Functional activity of NK-cells is evaluated by expression level and repertoire of killer cell immunoglobulin-like receptors (KIR). Current studies demonstrate that a patient’s KIR genotype affects the probability of achieving early and deep molecular responses to first- and second-generation TKIs, progression-free and overall survivals, and sustaining treatment-free remission. On that ground, KIR-genetic factors can be regarded as promising predictors of response to TKI therapy in CML. Early clinical studies, which dealt with monoclonal antibodies blocking the inhibitory KIR in order to increase NK-cell activity, revealed an acceptable safety profile and efficacy in some hematological diseases (such as acute myeloid leukemia, multiple myeloma, Т-cell lymphoma) if used in combination with cytostatic drugs or antitumor monoclonal antibodies. KIR genotype determination can contribute to the development of effective therapies of this malignant hematological tumor.

Keywords: genes of killer cell immunoglobulin-like receptors, tyrosine kinase inhibitors, treatment-free remission, chronic myeloid leukemia.

Received: November 8, 2022

Accepted: March 1, 2023

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