scholarly journals Overexpression of Enhancer of Zeste Homolog 2 Is Associated with Clinical Outcome in Acute Myeloid Leukemia Patients

2012 ◽  
Vol 23 ◽  
pp. ix349
Author(s):  
P. Lin ◽  
S. Yeh ◽  
L. Bai ◽  
C. Lin ◽  
C. Chiu
Leukemia ◽  
2015 ◽  
Vol 29 (7) ◽  
pp. 1485-1495 ◽  
Author(s):  
I Dzneladze ◽  
R He ◽  
J F Woolley ◽  
M H Son ◽  
M H Sharobim ◽  
...  

HemaSphere ◽  
2019 ◽  
Vol 3 (S1) ◽  
pp. 807-808
Author(s):  
Y.K. Lee ◽  
J. Lee ◽  
K. Jeon ◽  
M. Kim ◽  
B. Han ◽  
...  

2020 ◽  
Vol 29 (3) ◽  
pp. 387-397
Author(s):  
Yangli Zhao ◽  
Tingjuan Zhang ◽  
Yangjing Zhao ◽  
Jingdong Zhou

BACKGROUND: The runt-related transcription factor family (RUNXs) including RUNX1, RUNX2, and RUNX3 are key transcriptional regulators in normal hematopoiesis. RUNXs dysregulations caused by aberrant expression or mutation are frequently seen in various human cancers especially in acute myeloid leukemia (AML). OBJECTIVE: We systemically analyzed the expression of RUNXs and their relationship with clinic-pathological features and prognosis in AML patients. METHODS: Expression of RUNXs was analyzed between AML patients and normal controls from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) projects. Correlations between RUNXs expression and clinical features together with survival were further analyzed. RESULTS: All RUNXs expression in AML patients was significantly increased as compared with controls. RUNXs expression was found to be significantly associated with genetic abnormalities such as RUNX1 mutation, t(8;21) and inv(16)/t(16;16). By Kaplan-Meier analysis, only RUNX3 overexpression was associated with shorter overall survival (OS) and disease-free survival (DFS) among non-M3 AML patients. Notably, in high RUNX3 expression groups, patients received hematopoietic stem cell transplantation (HSCT) had markedly better OS and DFS than patients without HSCT among both all AML and non-M3 AML. In low RUNX3 expression groups, there were no significant differences in OS and DFS between HSCT and non-HSCT groups among both all AML and non-M3 AML. In addition, a total of 835 differentially expressed genes and 69 differentially expressed microRNAs were identified to be correlated with RUNX3 expression in AML. CONCLUSION: RUNXs overexpression was a frequent event in AML, and was closely associated with diverse genetic alterations. Moreover, RUNX3 expression may be associated with clinical outcome, and helpful for guiding treatment choice between HSCT and chemotherapy in AML.


Hematology ◽  
2020 ◽  
Vol 25 (1) ◽  
pp. 507-514
Author(s):  
Lu-Hong Xu ◽  
Jing-Wen Wang ◽  
Yin Wang ◽  
Feng-Ying Yang

2020 ◽  
Vol 4 (20) ◽  
pp. 5257-5268
Author(s):  
Yiyang Chen ◽  
Lina Marie Hoffmeister ◽  
Yasmin Zaun ◽  
Lucas Arnold ◽  
Kurt Werner Schmid ◽  
...  

Abstract Murine models of myeloid neoplasia show how leukemia infiltration alters the hematopoietic stem cell (HSC) niche to reinforce malignancy at the expense of healthy hematopoiesis. However, little is known about the bone marrow architecture in humans and its impact on clinical outcome. Here, we dissect the bone marrow niche in patients with acute myeloid leukemia (AML) at first diagnosis. We combined immunohistochemical stainings with global gene expression analyses from these AML patients and correlated them with clinical features. Mesenchymal stem and progenitor cells (MSPCs) lost quiescence and significantly expanded in the bone marrow of AML patients. Strikingly, their HSC- and niche-regulating capacities were impaired with significant inhibition of osteogenesis and bone formation in a cell contact–dependent manner through inhibition of cytoplasmic β-catenin. Assessment of bone metabolism by quantifying peripheral blood osteocalcin levels revealed 30% lower expression in AML patients at first diagnosis than in non-leukemic donors. Furthermore, patients with osteocalcin levels ≤11 ng/mL showed inferior overall survival with a 1-year survival rate of 38.7% whereas patients with higher osteocalcin levels reached a survival rate of 66.8%. These novel insights into the human AML bone marrow microenvironment help translate findings from preclinical models and detect new targets which might pave the way for niche-targeted therapies in AML patients.


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