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

ABSTRACT: Accumulating studies have proved EZH2 dysregulation mediated by mutation and expression in diverse human cancers including AML. However, the expression pattern of EZH2 remains controversial in acute myeloid leukaemia (AML). EZH1/2 expression and mutation were analysed in 200 patients with AML. EZH2 expression was significantly decreased in AML patients compared with normal controls but not for EZH1 expression. EZH2 mutation was identified three of the 200 AML patients (1.5%, 3/200), whereas none of the patients harboured EZH1 mutation (0%, 0/200). EZH2 expression and mutation were significantly associated with -7/del(7) karyotypes. Moreover, lower EZH2 expression was associated with older age, higher white blood cells, NPM1 mutation, CEBPA wild-type and WT1 wild-type. Patients with EZH2 mutation showed shorter overall survival (OS) and leukaemia-free survival (LFS) than patients without EHZ2 mutation after receiving autologous or allogeneic haematopoietic stem cell transplantation (HSCT). However, EZH2 expression has no effect on OS and LFS of AML patients. Notably, in EZH2 low group, patients undergone HSCT had significantly better OS and LFS compared with patients only received chemotherapy, whereas no significant difference was found in OS and LFS between chemotherapy and HSCT patients in EZH2 high group. Collectively, EZH2 dysregulation caused by mutation and under-expression identifies specific subtypes of AML EZH2 dysregulation may be acted as potential biomarkers predicting prognosis and guiding the treatment choice between transplantation and chemotherapy.

SUBMITTER: Chu MQ

PROVIDER: S-EPMC6991666 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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

Chu Ming-Qiang MQ Zhang Ting-Juan TJ Xu Zi-Jun ZJ Gu Yu Y Ma Ji-Chun JC Zhang Wei W Wen Xiang-Mei XM Lin Jiang J Qian Jun J Zhou Jing-Dong JD Zhou Jing-Dong JD

Journal of cellular and molecular medicine 20191203 2

Accumulating studies have proved EZH2 dysregulation mediated by mutation and expression in diverse human cancers including AML. However, the expression pattern of EZH2 remains controversial in acute myeloid leukaemia (AML). EZH1/2 expression and mutation were analysed in 200 patients with AML. EZH2 expression was significantly decreased in AML patients compared with normal controls but not for EZH1 expression. EZH2 mutation was identified three of the 200 AML patients (1.5%, 3/200), whereas none ...[more]

PMID: 31794134

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Project description:Changes in lipid metabolism affect numerous cellular processes that are relevant to cancer biology, including cell proliferation, death, differentiation and motility. In the phosphatidylcholine biosynthesis pathway, the conversion of lysophosphatidylcholine (LPC) to phosphatidylcholine is catalyzed by cytosolic enzymes of the LPC acyltransferase (LPCAT) family. A number of studies have demonstrated that LPCAT1 overexpression is a frequent event in diverse human cancer types, and that it is associated with unfavorable pathological characteristics and patient survival. The aim of the present study was to explore the prognostic role of the expression of LPCAT family members in acute myeloid leukemia (AML). Using Cox regression analysis, only LPCAT1 expression was identified as an independent prognostic biomarker in AML. In a cohort from The Cancer Genome Atlas, Kaplan-Meier analysis revealed that patients with AML and higher expression levels of LPCAT1 had shorter overall survival (OS) and leukemia-free survival (LFS) times compared with those with lower expression levels of LPCAT1. This was further confirmed using an independent cohort from the Gene Expression Omnibus. Using a third cohort comprising patients with AML and healthy volunteers, it was confirmed that LPCAT1 expression was significantly increased in newly diagnosed AML cases compared with healthy controls. Moreover, higher expression of LPCAT1 was associated with French-American-British subtype-M4/M5 and nucleophosmin 1 mutations. Notably, patients who underwent hematopoietic stem cell transplantation (HSCT) following induction therapy exhibited significantly longer OS and LFS times compared with patients who only received chemotherapy after induction therapy in the higher LPCAT1 expression group, whereas no significant differences in OS and LFS times were observed between the HSCT and chemotherapy groups among total cases of AML in the lower LPCAT1 expression group. These results suggest that patients with AML who exhibit higher LPCAT1 expression levels may benefit from HSCT. Collectively, the findings of the present study indicate that LPCAT1 expression may serve as an independent prognostic biomarker that can guide the choice between HSCT and chemotherapy in patients with AML.

Dataset Information

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

Publications

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

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