急性髓系白血病患者骨髓单个核细胞中EZH2、PTEN mRNA表达及其相关性
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摘要
目的观察急性髓系白血病(AML)患者骨髓单个核细胞中果蝇zeste基因增强子同源物2(EZH2)、张力蛋白同源的10号染色体缺失的磷酸酶基因(PTEN)mRNA表达变化,并分析二者的相关性。方法选择AML患者60例纳入AML组,因贫血、不明原因出血等行骨髓穿刺检查者20例为正常对照组。获取两组骨髓单个核细胞,采用实时荧光定量PCR法检测骨髓单个核细胞中的EZH2、PTEN mRNA,分析AML患者骨髓单个核细胞中EZH2、PTEN mRNA表达的相关性。结果 AML组骨髓单个核细胞中EZH2 mRNA相对表达量高于正常对照组,PTEN mRNA相对表达量低于正常对照组(P均<0.01)。AML患者骨髓单个核细胞中EZH2 mRNA与PTEN mRNA表达呈负相关(r=-0.694,P<0.05)。结论 AML患者骨髓单个核细胞中EZH2 mRNA高表达、PTEN mRNA低表达,且二者表达呈负相关;EZH2与PTEN可能参与了AML的发病,且二者之间可能存在一定的相互作用。
Objective To investigate the mRNA expression of enhancer of zeste homolog 2(EZH2) and phosphatase and tensin hemology deleted on chromosome ten gene(PTEN) in bone marrow mononuclear cells of patients with acute myeloid leukemia(AMI) and to analyze the correlation between them. Methods The mRNA expression of EZH2 and PTEN in the bone marrow mononuclear cells was quantified by real-time fluorescent quantitative PCR in 60 cases of AML patients(AML group) and 20 cases normal subjects undergoing bone marrow puncture because of anemia or unexplained bleeding(normal control group). The correlation between EZH2 and PTEN was analyzed. Results The expression of EZH2 mRNA in the bone marrow mononuclear cells of AML group was higher than that of the normal control group, while the expression of PTEN mRNA was significantly lower than that of the normal control group(both P<0.05). The EZH2 mRNA expression was negatively correlated with PTEN mRNA expression in bone marrow mononuclear cells of AML patients(r=-0.694, P<0.05). Conclusions EZH2 mRNA is highly expressed and PTEN mRNA is low expressed in the bone marrow mononuclear cells of AML patients, which are negatively correlated with each other; EZH2 and PTEN may be involved in the pathogenesis of AML, and there may be some interaction between them.
Objective To investigate the mRNA expression of enhancer of zeste homolog 2(EZH2) and phosphatase and tensin hemology deleted on chromosome ten gene(PTEN) in bone marrow mononuclear cells of patients with acute myeloid leukemia(AMI) and to analyze the correlation between them. Methods The mRNA expression of EZH2 and PTEN in the bone marrow mononuclear cells was quantified by real-time fluorescent quantitative PCR in 60 cases of AML patients(AML group) and 20 cases normal subjects undergoing bone marrow puncture because of anemia or unexplained bleeding(normal control group). The correlation between EZH2 and PTEN was analyzed. Results The expression of EZH2 mRNA in the bone marrow mononuclear cells of AML group was higher than that of the normal control group, while the expression of PTEN mRNA was significantly lower than that of the normal control group(both P<0.05). The EZH2 mRNA expression was negatively correlated with PTEN mRNA expression in bone marrow mononuclear cells of AML patients(r=-0.694, P<0.05). Conclusions EZH2 mRNA is highly expressed and PTEN mRNA is low expressed in the bone marrow mononuclear cells of AML patients, which are negatively correlated with each other; EZH2 and PTEN may be involved in the pathogenesis of AML, and there may be some interaction between them.
引文
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[9] Tesio M, Trinquand A, Ballerini P, et al. Age-related clinical and biological features of PTEN abnormalities in T-cell acute lymphoblastic leukaemia[J]. Leukemia, 2017,31(12):2594-2600.
[10] Short NJ, Rytting ME, Cortes JE. Acute myeloid leukaemia[J]. Lancet, 2018,392(10147):593-606.
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[12] Lu C, Han HD, Mangala LS, et al. Regulation of tumor angiogenesis by EZH2[J]. Cancer Cell, 2010,18(2):185-197.
[13] Nakagawa M, Kitabayashi I. Oncogenic roles of enhancer of zeste homolog 1/2 in hematological malignancies[J]. Cancer Sci, 2018,109(8):2342-2348.
[14] Herviou L, Cavalli G, Moreaux J. EZH2 is therapeutic target for personalized treatment in multiple myeloma[J]. Bull Cancer, 2018,105(9):804-819.
[15] Kim KH, Roberts CW. Targeting EZH2 in cancer [J]. Nat Med, 2016,22(2):128-134.
[16] Herviou L, Cavalli G, Cartron G, et al. EZH2 in normal hematopoiesis and hematological malignancies[J]. Oncotarget, 2016,7(3):2284-2296.
[17] Chen CY, Chen J, He L, et al. PTEN: tumor suppressor and metabolic regulator[J]. Front Endocrinol (Lausanne), 2018,9:338.
[18] Kaur M, Cole MD. MYC acts via the PTEN tumor suppressor to elicit autoregulation and genome-wide gene repression by activation of the Ezh2 methyltransferase[J]. Cancer Res, 2013,73(2):695-705.
[19] Zhang X, Jin T, Huang X, et al. Effects of the tumor suppressor PTEN on biological behaviors of activated pancreatic stellate cells in pancreatic fibrosis[J]. Exp Cell Res, 2018,373(1-2):132-144.
[20] 刘丽萍,徐文君,冉学红.EVI1基因在急性髓系白血病中对PTEN表达呈负相关[J].基因组学与应用生物,2016,35(11):2920-2924.
[2] Grimwade D, Ivey A, Huntly BJ. Molecular landscape of acute myeloid leukemia in younger adults and its clinical relevance[J]. Blood, 2016,127(1):29-41.
[3] Safaei S, Baradaran B, Hagh MF, et al. Double sword role of EZH2 in leukemia[J]. Biomed Pharmacother, 2018,98:626-635.
[4] Zhao K, He J, Wang YF, et al. EZH2-mediated epigenetic suppression of EphB3 inhibits gastric cancer proliferation and metastasis by affecting E-cadherin and vimentin expression[J]. Gene, 2018,686:118-124.
[5] Karakashev S, Zhu H, Wu S, et al. CARM1-expressing ovarian cancer depends on the histone methyltransferase EZH2 activity[J]. Nat Commun, 2018,9(1):631.
[6] Jones BA, Varambally S, Arend RC. Histone methyltransferase EZH2: a therapeutic target for ovarian cancer[J]. Mol Cancer Ther, 2018,17(3):591-602.
[7] Jayakumar R, Lanjewar S, Axiotis CA. Loss of PTEN and increased pAKT expression distinguishes aggressive low-grade neuroendocrine tumors[J]. Ann Clin Lab Sci, 2018,48(5):565-572.
[8] Lee YR, Chen M, Pandolfi PP. The functions and regulation of the PTEN tumour suppressor: new modes and prospects[J]. Nat Rev Mol Cell Biol, 2018,19(9):547-562.
[9] Tesio M, Trinquand A, Ballerini P, et al. Age-related clinical and biological features of PTEN abnormalities in T-cell acute lymphoblastic leukaemia[J]. Leukemia, 2017,31(12):2594-2600.
[10] Short NJ, Rytting ME, Cortes JE. Acute myeloid leukaemia[J]. Lancet, 2018,392(10147):593-606.
[11] Burnett A, Wetzler M, Lowenberg B. Therapeutic advances in acute myeloid leukemia[J]. J Clin Oncol, 2011,29(5):487-494.
[12] Lu C, Han HD, Mangala LS, et al. Regulation of tumor angiogenesis by EZH2[J]. Cancer Cell, 2010,18(2):185-197.
[13] Nakagawa M, Kitabayashi I. Oncogenic roles of enhancer of zeste homolog 1/2 in hematological malignancies[J]. Cancer Sci, 2018,109(8):2342-2348.
[14] Herviou L, Cavalli G, Moreaux J. EZH2 is therapeutic target for personalized treatment in multiple myeloma[J]. Bull Cancer, 2018,105(9):804-819.
[15] Kim KH, Roberts CW. Targeting EZH2 in cancer [J]. Nat Med, 2016,22(2):128-134.
[16] Herviou L, Cavalli G, Cartron G, et al. EZH2 in normal hematopoiesis and hematological malignancies[J]. Oncotarget, 2016,7(3):2284-2296.
[17] Chen CY, Chen J, He L, et al. PTEN: tumor suppressor and metabolic regulator[J]. Front Endocrinol (Lausanne), 2018,9:338.
[18] Kaur M, Cole MD. MYC acts via the PTEN tumor suppressor to elicit autoregulation and genome-wide gene repression by activation of the Ezh2 methyltransferase[J]. Cancer Res, 2013,73(2):695-705.
[19] Zhang X, Jin T, Huang X, et al. Effects of the tumor suppressor PTEN on biological behaviors of activated pancreatic stellate cells in pancreatic fibrosis[J]. Exp Cell Res, 2018,373(1-2):132-144.
[20] 刘丽萍,徐文君,冉学红.EVI1基因在急性髓系白血病中对PTEN表达呈负相关[J].基因组学与应用生物,2016,35(11):2920-2924.