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.
Mol Biol Rep. 2023 Jan;50(1):641-653. doi: 10.1007/s11033-022-08000-0. Epub 2022 Nov 12.
was to assess the role of C-KIT, TET1 and TET2 expression in the diagnosis and prognosis of acute myeloblastic leukemia (AML).
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.
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.
C-KIT, TET1, and TET2 could be used as possible useful biomarkers for the diagnosis of AML.
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。
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。
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。
C-KIT、TET1 和 TET2 可作为 AML 诊断的潜在有用生物标志物。