Abstract
Background Natural Killer (NK) cells are innate lymphoid cells that can be cytotoxic toward a large panel of solid tumors and hematological malignancies including chronic myeloid leukemia (CML). Such a cytotoxicity depends on various receptors. Killer immunoglobulin‐like receptors (KIR) belong to these receptors and are involved in maturation process, then in the activation abilities of NK cells. Methods: We investigated the prognostic impact of the KIR2DL5B genotype in 240 CML patients included in two clinical trials investigating tyrosine kinase inhibitors (TKI) discontinuation: STIM and STIM2. Results: After adjustment for standard risk factors in CML, we found that the inhibitory receptor KIR2DL5B‐positive genotype was independently related to a delayed second deep molecular remission (HR 0.54, 95% CI [0.32‐0.91], P = 0.02) after TKI rechallenge but not to time to first deep molecular remission or treatment‐free remission rates. Conclusion: These results suggest that KIR2DL5B could carry a role in lymphocyte‐mediated control of leukemic residual disease control in patient with CML relapse.
Highlights
Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder caused by the constitutively active chimeric BCR‐ABL1 tyrosine kinase
Time to first deep molecular response (DMR) ≥ 26 months (HR 0.58, 95% confidence interval (CI) [0.38‐0.88], P = 0.01) and KIR2DL5B‐positive status (HR 0.54, 95% confidence intervals (95% CI) [0.32‐0.91], P = 0.02) were associated with a longer delay before second DMR (Figure 1C) while treatments at recurrence were similar in both groups (Table 3) with a median follow‐up from relapse to last follow‐up examination for relapsing patients about 14 months (IQR 10‐15)
This study investigated, in a large cohort of chronic myeloid leukemia (CML) patients, Killer immunoglobulin‐like receptors (KIR) genotype prognostic effects with a focus on KIR2DL5B for stopping imatinib strategy
Summary
Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder caused by the constitutively active chimeric BCR‐ABL1 tyrosine kinase. The receptor KIR2DL5 belongs to KIR receptor family and possesses a unique combination of genetic, structural, and functional hallmarks that confer an inhibitory function when binding to its unknown ligand.[11] It is encoded by two genes, KIR2DL5A and KIR2DL5B, present in half of the Caucasian population.[12] The expression of KIR2DL5 has solely been described in CD8+ T cells and CD56dim NK subset.[13] In the setting of CML, KIR2DL5A and KIR2DL5B genotypes have been associated with a decrease in the rate of 12‐month molecular response 14 and 2‐year complete cytogenetic response.[15] Recently, the specific KIR2DL5B genotype has been shown to predict a bad prognosis through various outcomes in CML in a first‐line imatinib strategy, including transformation‐free survival, suggesting an important role in CML immune escape.[16]. We investigated the role of KIR2DL5B genotype with the objective to find a biomarker to better predict outcomes in a stopping imatinib strategy for CML
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