KIR-基因因素和对治疗的反应

Q4 Medicine
Елена Витальевна Кузьмич, И. Е. Павлова, Л. Н. Бубнова, С. С. Бессмельцев
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引用次数: 0

摘要

酪氨酸激酶抑制剂(TKIs)的开发及其临床应用显著改善了慢性髓性白血病(CML)患者的预后。约50%达到深度分子反应的患者符合安全停药TKI的条件。尽管取得了这些进展,但目前还没有可靠的生物标志物来预测TKI停药后的反应和持续无治疗缓解。由于TKIs不会破坏可导致复发的白血病干细胞,因此具有抗肿瘤活性的自然杀手(nk细胞)在CML中至关重要。nk细胞的功能活性是通过杀伤细胞免疫球蛋白样受体(KIR)的表达水平和库来评估的。目前的研究表明,患者的KIR基因型影响对第一代和第二代TKIs实现早期和深度分子反应的可能性,无进展和总生存率,以及维持无治疗缓解。基于此,kir遗传因素可被视为CML患者对TKI治疗反应的有希望的预测因素。早期的临床研究涉及单克隆抗体阻断抑制KIR以增加nk细胞活性,表明如果与细胞抑制剂药物或抗肿瘤单克隆抗体联合使用,在某些血液病(如急性髓性白血病、多发性骨髓瘤、Т-cell淋巴瘤)中具有可接受的安全性和有效性。确定KIR基因型有助于开发有效的治疗这种恶性血液肿瘤的方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
KIR-генетические факторы и ответ на терапию ингибиторами тирозинкиназ при хроническом миелоидном лейкозе
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.
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CiteScore
0.80
自引率
0.00%
发文量
20
审稿时长
12 weeks
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