Killer immunoglobulin-like receptor genotypes and chronic myeloid leukemia outcomes after imatinib cessation for treatment-free remission
Killer immunoglobulin-like receptor genotypes and chronic myeloid leukemia outcomes after imatinib cessation for treatment-free remission
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DOI：
10.1002/cam4.2371
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发表时间：
2019-07-09
期刊：
影响因子：
4
通讯作者：
Mahon, Francois-Xavier
中科院分区：
文献类型：
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作者：
Dumas, Pierre-Yves;Berard, Emilie;Mahon, Francois-Xavier
自然杀伤细胞（NK）是一种先天淋巴样细胞，对大量实体瘤和包括慢性髓性白血病（CML）在内的血液系统恶性肿瘤具有细胞毒性。这种细胞毒性取决于不同的受体。杀伤免疫球蛋白样受体（KIR）属于这些受体，参与NK细胞的成熟过程，进而参与NK细胞的活化能力。方法：我们研究了KIR2DL5B基因型对240名CML患者预后的影响，这些患者参与了两项研究酪氨酸激酶抑制剂（TKI）停药的临床试验：STIM和STIM2。结果：在调整CML的标准危险因素后，我们发现抑制受体kir2dl5b阳性基因型与TKI再挑战后延迟的第二次深度分子缓解（HR 0.54, 95% CI [0.32-0.91], P = 0.02）独立相关，但与第一次深度分子缓解时间或无治疗缓解率无关。结论：这些结果提示KIR2DL5B可能在CML复发患者淋巴细胞介导的白血病残留疾病控制中发挥作用。
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.