TY - JOUR
T1 - Down-regulation of EZH2 expression in myelodysplastic syndromes
AU - Cabrero, Monica
AU - Wei, Yue
AU - Yang, Hui
AU - Ganan-Gomez, Irene
AU - Bohannan, Zach
AU - Colla, Simona
AU - Marchesini, Matteo
AU - Bravo, Guillermo Montalban
AU - Takahashi, Koichi
AU - Bueso-Ramos, Carlos
AU - Garcia-Manero, Guillermo
N1 - Funding Information:
MC is funded by the Fundacion Alfonso Martin-Escudero. GGM is supported by The University of Texas MD Anderson Cancer Center Support Grant P30CA016672. GGM is also supported by the Edward P. Evans Foundation, the Fundacion Ramon Areces, grant RP100202 from the Cancer Prevention & Research Institute of Texas (CPRIT), and by generous philanthropic contributions to MD Anderson’s MDS/AML Moon Shot Program. GGM partially supported by the Dr. Kenneth B. McCredie Chair in Clinical Leukemia Research endowment.
Funding Information:
MC is funded by the Fundacion Alfonso Martin-Escudero . GGM is supported by The University of Texas MD Anderson Cancer Center Support Grant P30CA016672 . GGM is also supported by the Edward P. Evans Foundation , the Fundacion Ramon Areces , grant RP100202 from the Cancer Prevention & Research Institute of Texas (CPRIT), and by generous philanthropic contributions to MD Anderson’s MDS/AML Moon Shot Program . GGM partially supported by the Dr. Kenneth B. McCredie Chair in Clinical Leukemia Research endowment.
Publisher Copyright:
© 2016 Elsevier Ltd.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - EZH2 genetic mutations are common in myelodysplastic syndrome (MDS), which implies that this gene has a pathophysiological role in the disease. To further characterize molecular alterations of EZH2, and their potential prognostic impact in MDS, we assessed EZH2 RNA expression in primary bone marrow CD34+ cells from 78 patients.We found that 47% of patients have reduced EZH2 expression compared to normal controls. Further analyses revealed that EZH2 is significantly underexpressed in patients bearing chromosome 7 or 7q deletions (7-alt) when compared to controls, diploid patients, and patients with other cytogenetic alterations (p < 0.05). In survival analysis, we found a non-significant trend toward overall survival (OS) being better among patients with EZH2 underexpression (median OS 55 vs. 36 months; p = 0.71). Importantly, this trend became significant when the analysis was restricted to the subset of cases without alterations in chromosome 7 (62 vs. 36 months; p = 0.033).Furthermore, our previous work has identified a spectrum of innate immune genes in MDS CD34+ cells that are deregulated via abnormal promoter histone methylation. Because EZH2 is a key regulator of histone methylation, we assessed the relationship between deregulation of these genes and EZH2 underexpression. We observed that the mRNA levels of 11 immune genes were higher in the EZH2 underexpression group and that immune gene expression was significantly higher in patients with concomitant EZH2 underexpression and KDM6B (also known as JMJD3, an H3K27 demethylase) overexpression.Taken together, these data indicate that EZH2 underexpression may have unique impact on the molecular pathogenesis and prognosis in MDS and be an important marker for patients without chromosome 7 alteration.
AB - EZH2 genetic mutations are common in myelodysplastic syndrome (MDS), which implies that this gene has a pathophysiological role in the disease. To further characterize molecular alterations of EZH2, and their potential prognostic impact in MDS, we assessed EZH2 RNA expression in primary bone marrow CD34+ cells from 78 patients.We found that 47% of patients have reduced EZH2 expression compared to normal controls. Further analyses revealed that EZH2 is significantly underexpressed in patients bearing chromosome 7 or 7q deletions (7-alt) when compared to controls, diploid patients, and patients with other cytogenetic alterations (p < 0.05). In survival analysis, we found a non-significant trend toward overall survival (OS) being better among patients with EZH2 underexpression (median OS 55 vs. 36 months; p = 0.71). Importantly, this trend became significant when the analysis was restricted to the subset of cases without alterations in chromosome 7 (62 vs. 36 months; p = 0.033).Furthermore, our previous work has identified a spectrum of innate immune genes in MDS CD34+ cells that are deregulated via abnormal promoter histone methylation. Because EZH2 is a key regulator of histone methylation, we assessed the relationship between deregulation of these genes and EZH2 underexpression. We observed that the mRNA levels of 11 immune genes were higher in the EZH2 underexpression group and that immune gene expression was significantly higher in patients with concomitant EZH2 underexpression and KDM6B (also known as JMJD3, an H3K27 demethylase) overexpression.Taken together, these data indicate that EZH2 underexpression may have unique impact on the molecular pathogenesis and prognosis in MDS and be an important marker for patients without chromosome 7 alteration.
KW - EZH2
KW - Epigenetics
KW - Histone methylation
KW - Myelodysplastic syndromes
UR - http://www.scopus.com/inward/record.url?scp=84960109315&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84960109315&partnerID=8YFLogxK
U2 - 10.1016/j.leukres.2016.02.009
DO - 10.1016/j.leukres.2016.02.009
M3 - Article
C2 - 26970171
AN - SCOPUS:84960109315
SN - 0145-2126
VL - 44
SP - 1
EP - 7
JO - Leukemia Research
JF - Leukemia Research
ER -