细胞因子 rs361525、rs1800750、rs1800629、rs1800896、rs1800872、rs1800795、rs1800470 和 rs2430561 单核苷酸多态性与急性髓细胞白血病的预后因素有关。
Cytokine rs361525, rs1800750, rs1800629, rs1800896, rs1800872, rs1800795, rs1800470, and rs2430561 SNPs in relation with prognostic factors in acute myeloid leukemia.
机构信息
Genetics Laboratory, Center for Advanced Medical and Pharmaceutical Research, University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, Târgu Mureș, Romania.
Department of Medical Genetics, University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, Târgu Mureș, Romania.
出版信息
Cancer Med. 2019 Sep;8(12):5492-5506. doi: 10.1002/cam4.2424. Epub 2019 Aug 1.
BACKGROUND
Cytokines were correlated with survival and disease progression in acute myeloid leukemia (AML). We aimed to evaluate the multivariate effect of TNF-α rs361525, rs1800750, rs1800629, IL-10 rs1800896, rs1800872, IL-6 rs1800795, TGF-β1 rs1800470, IFN-γ rs2430561 single nucleotide polymorphisms (SNPs) on AML risk, the multivariate effect of SNPs on overall survival (OS) in AML and the association between the investigated SNPs and prognostic factors in AML.
METHODS
All SNPs were genotyped in 226 adult AML cases and 406 healthy individuals. AML patients were investigated for FLT3 (ITD, D835), DNMT3A (R882), and NPM1 type A mutations.
RESULTS
Univariate analysis revealed that age above 65 years had a negative influence on survival (P < .001). The presence of the rs1800750 variant genotype (P = .005) or FLT3-ITD mutation (P = .009) in a cytogenetic high-risk group (P = .003) negatively influenced OS. A negative association was observed between Eastern Cooperative Oncologic Group Scale status > 2, lactate dehydrogenase (LDH) level, platelet (PLT) count <40 000 cells/mm , and OS. Multivariate Cox regression analysis showed that the presence of the rs1800750 variant genotype was a risk factor for death (P = .007), and that blast percentage, LDH level (≥600 IU/L), and cytogenetic high-risk were independent significant predictors for death in AML (P = .04, corrected HR = 1.20; P = .022, corrected HR = 1.24; P = .021, corrected HR = 1.34, respectively).
CONCLUSIONS
Age above 65 years, PLT count, TNF-α rs1800750 variant genotype, blast percentage, LDH level, and cytogenetic high-risk may be used as independent risk factors to assess AML mortality.
背景
细胞因子与急性髓系白血病（AML）的生存和疾病进展相关。我们旨在评估 TNF-α rs361525、rs1800750、rs1800629、IL-10 rs1800896、rs1800872、IL-6 rs1800795、TGF-β1 rs1800470、IFN-γ rs2430561 单核苷酸多态性（SNP）对 AML 风险的多变量影响、SNP 对 AML 总生存期（OS）的多变量影响，以及所研究的 SNP 与 AML 预后因素之间的关系。
方法
在 226 例成人 AML 病例和 406 例健康个体中对所有 SNP 进行了基因分型。对 AML 患者进行了 FLT3（ITD、D835）、DNMT3A（R882）和 NPM1 型 A 突变的检测。
结果
单因素分析显示，年龄大于 65 岁对生存有负面影响（P <.001）。在细胞遗传学高危组中存在 rs1800750 变异基因型（P =.005）或 FLT3-ITD 突变（P =.009），以及 OS 不良（P =.003）。Eastern Cooperative Oncologic Group Scale 状态>2、乳酸脱氢酶（LDH）水平、血小板（PLT）计数<40000 个/毫米 与 OS 呈负相关。多因素 Cox 回归分析显示，rs1800750 变异基因型的存在是死亡的危险因素（P =.007），而 blast%、LDH 水平（≥600IU/L）和细胞遗传学高危是 AML 死亡的独立显著预测因素（P=.04，校正 HR=1.20；P=.022，校正 HR=1.24；P=.021，校正 HR=1.34）。
结论
年龄大于 65 岁、PLT 计数、TNF-α rs1800750 变异基因型、blast%、LDH 水平和细胞遗传学高危可作为评估 AML 死亡率的独立危险因素。
Zotero 插件