Epigenetic changes in FOXO3 and CHEK2 genes and their correlation with clinicopathological findings in myelodysplastic syndromes.
DNA hypermethylation
Epigenetic changes
High-resolution melting
Myelodysplastic syndromes
Real-time PCR
Journal
Hematology/oncology and stem cell therapy
ISSN: 2589-0646
Titre abrégé: Hematol Oncol Stem Cell Ther
Pays: Saudi Arabia
ID NLM: 101468532
Informations de publication
Date de publication:
Dec 2020
Dec 2020
Historique:
received:
02
09
2019
accepted:
07
11
2019
pubmed:
29
3
2020
medline:
27
3
2021
entrez:
29
3
2020
Statut:
ppublish
Résumé
Myelodysplastic syndromes (MDSs) are a heterogeneous disease in terms of clinical course and response to therapy. Epigenetic changes are the primary mechanism of MDS pathogenesis. FOXO3 and CHEK2 genes play significant roles in normal cellular mechanisms and are also known as tumor suppressor genes. We aimed to clarify the correlation of epigenetic changes in these genes with clinicopathologic findings in MDS. A total of 54 newly diagnosed MDS patients referred to Shariati and Firouzgar Hospitals (Tehran, Iran) were included in the study from 2013 to 2015, comprising the following cases: 26 with refractory cytopenia with unilineage dysplasia, 10 with refractory cytopenia with multilineage dysplasia, four refractory anemia with excess blasts-1 (RAEB-1), 11 refractory anemia with excess blasts-2 (RAEB-2), and three MDS associated with isolated deletion (5q-). Risk groups were determined according to the Revised International Prognostic Scoring System (IPSS-R). The methylation status of CHEK2 and FOXO3 promoters were determined by methylation-sensitive high-resolution melting analysis of sodium bisulfite-converted DNA. Expressions of CHEK2, FOXO3, and GAPDH were measured by quantitative real-time polymerase chain reaction and fold changes were calculated using the ΔΔCT method. Statistical analysis revealed no promoter methylation of CHEK2 and FOXO3 in healthy control specimens. FOXO3 promoter methylation was associated with high-risk World Health Organization subgroups (p = .017), high-risk IPSS-R (p = .007), high-risk cytogenetics (p = .045), and more than 5% blasts in bone marrow (p = .001). CHEK2 promoter methylation was correlated with more than 5% blasts in bone marrow (p = .009). Promoter methylation of CHEK2 and especially FOXO3 is associated with adverse clinicopathological findings and disease progression in MDS.
Sections du résumé
OBJECTIVES/BACKGROUND
OBJECTIVE
Myelodysplastic syndromes (MDSs) are a heterogeneous disease in terms of clinical course and response to therapy. Epigenetic changes are the primary mechanism of MDS pathogenesis. FOXO3 and CHEK2 genes play significant roles in normal cellular mechanisms and are also known as tumor suppressor genes. We aimed to clarify the correlation of epigenetic changes in these genes with clinicopathologic findings in MDS.
METHODS
METHODS
A total of 54 newly diagnosed MDS patients referred to Shariati and Firouzgar Hospitals (Tehran, Iran) were included in the study from 2013 to 2015, comprising the following cases: 26 with refractory cytopenia with unilineage dysplasia, 10 with refractory cytopenia with multilineage dysplasia, four refractory anemia with excess blasts-1 (RAEB-1), 11 refractory anemia with excess blasts-2 (RAEB-2), and three MDS associated with isolated deletion (5q-). Risk groups were determined according to the Revised International Prognostic Scoring System (IPSS-R). The methylation status of CHEK2 and FOXO3 promoters were determined by methylation-sensitive high-resolution melting analysis of sodium bisulfite-converted DNA. Expressions of CHEK2, FOXO3, and GAPDH were measured by quantitative real-time polymerase chain reaction and fold changes were calculated using the ΔΔCT method.
RESULTS
RESULTS
Statistical analysis revealed no promoter methylation of CHEK2 and FOXO3 in healthy control specimens. FOXO3 promoter methylation was associated with high-risk World Health Organization subgroups (p = .017), high-risk IPSS-R (p = .007), high-risk cytogenetics (p = .045), and more than 5% blasts in bone marrow (p = .001). CHEK2 promoter methylation was correlated with more than 5% blasts in bone marrow (p = .009).
CONCLUSIONS
CONCLUSIONS
Promoter methylation of CHEK2 and especially FOXO3 is associated with adverse clinicopathological findings and disease progression in MDS.
Identifiants
pubmed: 32217071
pii: S1658-3876(20)30042-X
doi: 10.1016/j.hemonc.2019.11.004
pii:
doi:
Substances chimiques
FOXO3 protein, human
0
Forkhead Box Protein O3
0
Checkpoint Kinase 2
EC 2.7.1.11
CHEK2 protein, human
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
214-219Informations de copyright
Copyright © 2020 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors report no conflicts of interest.