Higher EZH2 expression is associated with extramedullary infiltration in acute myeloid leukemia
- 296 Downloads
Accumulating evidence indicates that enhancer of zeste homolog 2 (EZH2) promotes the metastatic ability of solid tumors, but the role of EZH2 in extramedullary infiltration (EMI) in acute myeloid leukemia (AML) has not been thoroughly explored. In the present study, we investigated the possible association between EZH2 and EMI. We found that the messenger RNA (mRNA) and protein expression levels of EZH2 in AML patients were both significantly higher than in idiopathic thrombocytopenic purpura (ITP) patients. Furthermore, a positive correlation between EZH2 mRNA expression and percentage of peripheral blood blasts wa s found in AML patients (r = 0.404, p = 0.009). The migratory capacities of Kasumi-1 and HL-60, which both show a high level of EZH2 expression, were markedly higher than those of U937 and KG-1α. In contrast, silencing of EZH2 resulted in reduction in proliferation and migration ability and an increase in apoptosis. The latter observation was accompanied by reduced expression of associated proteins p-ERK, p-cmyc, and matrix metalloproteinase 2 (MMP-2) and an increase in epithelial cadherin (E-cadherin). These data suggest that higher expression of EZH2 may be associated with extramedullary infiltration in acute myeloid leukemia and affect pathogenesis via activation of the p-ERK/p-cmyc/MMP-2 and E-cadherin signaling pathways.
KeywordsAcute myeloid leukemia EZH2 Extramedullary infiltration p-ERK/p-cmyc/MMP-2
Fanyi Meng, Qiuhua Zhu, and Lingxiu Zhang conceptualized and designed the study, collected and analyzed data, and drafted the paper; Qiuhua Zhu and Lingxiu Zhang performed the experiments. Qiuhua Zhu and Lingxiu Zhang contributed equally to this work. Fanyi Meng and Hongsheng Zhou helped to revise the paper. All authors read and approved the final manuscript.
This work was supported by Guangzhou Science and Technology Plan Projects (No. 2013J4100109) and the Specialized Research Fund for the Doctoral Program of Higher Education (No. 20124433110001). National Natural Science Foundation of China (No. 81500138), Natural Science Foundation of Guangdong Province, China (No. 2014A030313270), Medical Research Foundation of Guangdong Province, China (No. B2014250).
Compliance with ethical standards
Conflicts of interest
- 5.Byrd JC, Weiss RB, Arthur DC, Lawrence D, Baer MR, Davey F, et al. Extramedullary leukemia adversely affects hematologic complete remission rate and overall survival in patients with t(8;21)(q22;q22): results from Cancer and Leukemia Group B 8461. J Clin Oncol. 1997;15:466–75.CrossRefPubMedGoogle Scholar
- 8.Kim SH, Yang WI, Min YH, Ko YH, Yoon SO. The role of the polycomb repressive complex pathway in T and NK cell lymphoma: biological and prognostic implications. Tumor Biol. 2015.Google Scholar
- 9.Xiaojing Yang RKMK, Miller PBOT: CDKN1C(p57KIP2) is a direct target of EZH2 and suppressed by multiple epigenetic mechanisms in breast cancer cellsGoogle Scholar
- 24.Fiskus W, Wang Y, Sreekumar A, Buckley KM, Shi H, Jillella A, et al. Combined epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin a and the histone deacetylase inhibitor panobinostat against human AML cells. Blood. 2009;114:2733–43.CrossRefPubMedPubMedCentralGoogle Scholar
- 33.Janowska-Wieczorek A, Marquez LA, Matsuzaki A, Hashmi HR, Larratt LM, Boshkov LM, et al. Expression of matrix metalloproteinases (MMP-2 and -9) and tissue inhibitors of metalloproteinases (TIMP-1 and -2) in acute myelogenous leukaemia blasts: comparison with normal bone marrow cells. Br J Haematol. 1999;105:402–11.CrossRefPubMedGoogle Scholar
- 34.Yasuda T. MAP kinase cascades in antigen receptor signaling and physiology. Curr Top Microbiol Immunol. 2015;393:211–31.Google Scholar