Higher EZH2 expression is associated with extramedullary infiltration in acute myeloid leukemia

Abstract

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.

EZH2 dysregulation: Potential biomarkers predicting prognosis and guiding treatment choice in acute myeloid leukaemia

“…However, the expression pattern of EZH2 remains controversial in AML. 17 In contrast, Göllner et al demonstrated that loss of the histone methyltransferase EZH2 17 In addition, EZH2 silencing resulted in decreased proliferation and migration ability and increased apoptosis, suggesting its oncogenic role in AML.…”

“…17 In addition, EZH2 silencing resulted in decreased proliferation and migration ability and increased apoptosis, suggesting its oncogenic role in AML. 17 In contrast, Göllner et al demonstrated that loss of the histone methyltransferase EZH2…”

“…[12][13][14][15] In AML, EZH2 mutation was associated with −7/del(7q) and low bone marrow blast percentage but not affected prognosis. 17 In addition, EZH2 silencing resulted in decreased proliferation and migration ability and increased apoptosis, suggesting its oncogenic role in AML. 17 In addition, EZH2 silencing resulted in decreased proliferation and migration ability and increased apoptosis, suggesting its oncogenic role in AML.…”

“…16 Recently, Zhu et al showed that overexpression of EZH2 was a frequent event and was associated with extramedullary infiltration in AML. 17 However, Göllner et al demonstrated that loss of the histone methyltransferase EZH2 induced resistance to multiple drugs in AML, indicating it may play as tumour suppressor gene in AML. 17 However, Göllner et al demonstrated that loss of the histone methyltransferase EZH2 induced resistance to multiple drugs in AML, indicating it may play as tumour suppressor gene in AML.…”

Roles of Polycomb gene EED in pathogenesis and prognosis of acute myeloid leukemia and diffuse large B cell lymphoma

“…The roles of PcG genes in LAML are elusive. High expression of EZH2 gene, coding PRC2 catalytic subunit, is associated with extramedullary infiltration in LAML and EZH2 silencing suppresses cell proliferation, cell migration and increases cell apoptosis in LAML through inhibiting MMP2 expression and increasing E-cadherin expression (Zhu et al 2016). However, lower EZH2 expression also correlates with poorer prognosis of LAML patients due to loss of EZH2 inhibits the expression of HOX gene and results in enhancing chemo-resistance of LAML cell lines (Gollner et al 2017).…”