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C-KIT、TET1 和 TET2 基因表达在急性髓系白血病中的预后作用。

The prognostic role of C-KIT, TET1 and TET2 gene expression in Acute Myeloid Leukemia.

机构信息

Clinical pathology Department, National Cancer Institute, Cairo University, Giza, Egypt.

Medical Biochemistry and molecular biology, Cancer Biology Department, National Cancer Institute, Cairo University, Giza, Egypt.

出版信息

Mol Biol Rep. 2023 Jan;50(1):641-653. doi: 10.1007/s11033-022-08000-0. Epub 2022 Nov 12.

Abstract

AIM

was to assess the role of C-KIT, TET1 and TET2 expression in the diagnosis and prognosis of acute myeloblastic leukemia (AML).

METHODS

The expression levels of C-KIT, TET1 and TET2 were assessed in the bone marrow (BM) aspirate of 152 AML patients compared to 20 healthy control using quantitative real-time polymerase chain reaction (qRT-PCR). Data were correlated with the clinico-pathological features of the patients, response to treatment, disease-free survival (DFS), and overall survival (OS) rates.

RESULTS

C-KIT, TET1 and TET2 were significantly upregulated in AML patients [0.25 (0-11.6), 0.0113 (0-3.301), and 0.07 (0-4); respectively], compared to the control group [0.013 (0.005-0.250), P < 0.001, 0.001 (0-0.006), P < 0.001, and 0.02 (0.008-0.055), P = 0.019; respectively]. The sensitivity, specificity, and area under curve of of C-KIT were (48.7%, 100%, 0.855; respectively, P = 0.001), and that of TET1 were (63.4%, 100%, 0.897; respectively, P = 0.001), while that of TET2 were (56.8%, 100%, 0.766; respectively, P = 0.019). When combining the three markers, the sensitivity was 77.5%, however it reached the highest sensitivity (78.6%) and specificity (100%) when combining both c-KIT + TET1 together for the diagnosis of AML. C-KIT overexpression associated with shorter DFS (P = 0.05) and increased incidence of relapse (P = 0.019). Lymph nodes involvement [HR = 2.200, P = 0.005] is an independent risk factor for shorter OS rate of AML patients. Increased BM blast % [HR = 7.768, P = 0.002], and FLT3-ITD mutation [HR = 2.989, P = 0.032] are independent risk factors for shorter DSF rate of the patients.

CONCLUSION

C-KIT, TET1, and TET2 could be used as possible useful biomarkers for the diagnosis of AML.

摘要

目的

评估 C-KIT、TET1 和 TET2 表达在急性髓系白血病(AML)诊断和预后中的作用。

方法

采用实时定量聚合酶链反应(qRT-PCR)比较 152 例 AML 患者和 20 例健康对照者骨髓抽吸物中 C-KIT、TET1 和 TET2 的表达水平。将数据与患者的临床病理特征、治疗反应、无病生存(DFS)和总生存(OS)率相关联。

结果

与对照组相比,AML 患者 C-KIT、TET1 和 TET2 表达明显上调[0.25(0-11.6)、0.0113(0-3.301)和 0.07(0-4)],P<0.001,0.001(0-0.006),P<0.001 和 0.02(0.008-0.055),P=0.019]。C-KIT 的灵敏度、特异性和曲线下面积分别为(48.7%,100%,0.855;P=0.001),TET1 分别为(63.4%,100%,0.897;P=0.001),而 TET2 分别为(56.8%,100%,0.766;P=0.019)。当结合三种标志物时,灵敏度为 77.5%,但当 C-KIT+TET1 联合用于 AML 诊断时,灵敏度(78.6%)和特异性(100%)最高。C-KIT 过表达与较短的 DFS(P=0.05)和更高的复发率(P=0.019)相关。淋巴结受累[HR=2.200,P=0.005]是 AML 患者 OS 率较短的独立危险因素。骨髓原始细胞比例增加[HR=7.768,P=0.002]和 FLT3-ITD 突变[HR=2.989,P=0.032]是患者 DFS 率较短的独立危险因素。

结论

C-KIT、TET1 和 TET2 可作为 AML 诊断的潜在有用生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/913d/9884250/2e3c1a255816/11033_2022_8000_Fig2_HTML.jpg

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