Clinical significance of BCL2L10 expression and promoter methylation in myelodysplastic syndrome

Yueru JI; Li LIU; Xueqian YAN; Guohui LI; Yi CHEN; Yangping ZHANG; Weiwei QIN

doi:10.16016/j.1000-5404.202005142

您当前的位置：

首页 >

文章列表页 >

Clinical significance of BCL2L10 expression and promoter methylation in myelodysplastic syndrome

更新时间：2026-01-09

- Clinical significance of BCL2L10 expression and promoter methylation in myelodysplastic syndrome
- Journal of Third Military Medical University Vol. 42, Issue 17, Pages: 1687-1692(2020)
- 作者机构：
- 作者简介：
- 基金信息：
- DOI：10.16016/j.1000-5404.202005142
  CLC：
- Received：18 May 2020，
  
  Published：15 September 2020
- 稿件说明：
移动端阅览
Yueru JI, Li LIU, Xueqian YAN, et al. Clinical significance of BCL2L10 expression and promoter methylation in myelodysplastic syndrome[J]. Journal of Third Military Medical University, 2020, 42(17): 1687-1692.
DOI：

Yueru JI, Li LIU, Xueqian YAN, et al. Clinical significance of BCL2L10 expression and promoter methylation in myelodysplastic syndrome[J]. Journal of Third Military Medical University, 2020, 42(17): 1687-1692. DOI： 10.16016/j.1000-5404.202005142.

摘要

Abstract

Objective

To investigate the clinical significance of BCL2L10 expression and promoter methylation status in patients with myelodysplastic syndrome (MDS).

Methods

andnbsp;Real-time PCR was performed to detect the expression level of BCL2L10 in bone marrow specimens from 56 MDS patients and 30 non-leukemia control patients. According to the results of International Prognostic Scor

ing System-Revised (IPSS-R)

the MDS patients were divided into low/medium risk group (IPSS-R score ≤4.5

=33) and high-risk MDS group (IPSS-R score

4.5

=23). Methylation specific PCR (MSP) was employed to analyze the methylation status of the promoter region of BCL2L10 gene. The relationship of the expression level of BCL2L10 with prognosis was analyzed in the subjects of these MDS patients and those from the GEPIA database.

Results

andnbsp;The expression of BCL2L10 was significantly lower in the MDS patients than the non-leukemia control group (

P＞0.05

)

and the level in the high-risk MDS subgroup was obviously lower than that in the non-leukemia control group and the low/moderate risk MDS subgroup (

P＞0.05

). The expression of BCL2L10 was regulated by methylation. The positive rate of methylation in BCL2L10 gene promoter was remarkably higher in the high-risk MDS patients than the non-leukemia control group (56.52%

36.67%

P＞0.05

) and the low/moderate risk subgroup (56.52%

30.30%

P＞0.05

). The methylation status of BCL2L10 gene promoter was closely related to the risk stratification of MDS patients (

Chi

-square=5.79

P＞0.05

). But age and sex had no such significant difference with (

P＞0.05

). Among the 24 patients who were not treated with methylation drugs

the 3-year survival rate of patients with high expression of BCL2L10 was lower than that of patients with low expression of BCL2L10 (83.3%

50.0%). For the subjects from the GEPIA database

those with lower BCL2L10 expression level had poorer prognosis than those with higher expression

but there was no statistical difference (

P＞0.05

Conclusion

andnbsp;The expression of BCL2L10 gene and its methylation status can be used as one of the indexes of prognosis in MDS.

关键词

Keywords

references

LINDSTEN T ROSS A J KING A The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues Mol Cell 2000 6 6 1389 1399 10.1016/s1097-2765(00)00136-2 LINDSTEN T, ROSS A J, KING A, et al . The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues[J ] . Mol Cell, 2000, 6(6): 1389-1399. DOI:10.1016/s1097-2765(00)00136-2.

LEE S Y KWON J WOO J H Bcl2l10 mediates the proliferation, invasion and migration of ovarian cancer cells Int J Oncol 2020 56 2 618 629 10.3892/ijo.2019.4949 LEE S Y, KWON J, WOO J H, et al . Bcl2l10 mediates the proliferation, invasion and migration of ovarian cancer cells[J ] . Int J Oncol, 2020, 56(2): 618-629. DOI:10.3892/ijo.2019.4949.

WU H L JEFFREY MEDEIROS L YOUNG K H Apoptosis signaling and BCL-2 pathways provide opportunities for novel targeted therapeutic strategies in hematologic malignances Blood Rev 2017 32 1 8 28 10.1016/j.blre.2017.08.004 WU H L, JEFFREY MEDEIROS L, YOUNG K H. Apoptosis signaling and BCL-2 pathways provide opportunities for novel targeted therapeutic strategies in hematologic malignances[J]. Blood Rev, 2017, 32(1): 8-28. DOI:10.1016/j.blre. 2017.08.004.

NOUGAREDE A POPGEORGIEV N KASSEM L Breast cancer targeting through inhibition of the endoplasmic reticulum-based apoptosis regulator Nrh/BCL2L10 Cancer Res 2018 78 6 1404 1417 10.1158/0008-5472.CAN-17-0846 NOUGAREDE A, POPGEORGIEV N, KASSEM L, et al . Breast cancer targeting through inhibition of the endoplasmic reticulum-based apoptosis regulator Nrh/BCL2L10[J ] . Cancer Res, 2018, 78(6): 1404-1417. DOI:10.1158/0008-5472.CAN-17-0846.

BAI Y WANG J HAN J BCL2L10 inhibits growth and metastasis of hepatocellular carcinoma both in vitro and in vivo Mol Carcinog 2017 56 3 1137 1149 10.1002/mc.22580 BAI Y, WANG J, HAN J, et al . BCL2L10 inhibits growth and metastasis of hepatocellular carcinoma both in vitro and in vivo [J ] . Mol Carcinog, 2017, 56(3): 1137-1149. DOI:10.1002/mc.22580.

XU J D FURUYA T CAO X X Loss of BCL2L10 protein expression as prognostic predictor for poor clinical outcome in gastric carcinoma Histopathology 2010 57 6 814 824 10.1111/j.1365-2559.2010.03720.x XU J D, FURUYA T, CAO X X, et al . Loss of BCL2L10 protein expression as prognostic predictor for poor clinical outcome in gastric carcinoma[J ] . Histopathology, 2010, 57(6): 814-824. DOI:10.1111/j.1365-2559.2010.03720.x.

VIDAL V ROBERT G GOURSAUD L BCL2L10 positive cells in bone marrow are an independent prognostic factor of azacitidine outcome in myelodysplastic syndrome and acute myeloid leukemia Oncotarget 2017 8 29 47103 47109 10.18632/oncotarget.17482 VIDAL V, ROBERT G, GOURSAUD L, et al . BCL2L10 positive cells in bone marrow are an independent prognostic factor of azacitidine outcome in myelodysplastic syndrome and acute myeloid leukemia[J ] . Oncotarget, 2017, 8(29): 47103-47109. DOI:10.18632/oncotarget.17482.

FABIANI E LEONE G GIACHELIA M Analysis of genome-wide methylation and gene expression induced by 5-aza-2′-deoxycytidine identifies BCL2L10 as a frequent methylation target in acute myeloid leukemia Leuk Lymphoma 2010 51 12 2275 2284 10.3109/10428194.2010.528093 FABIANI E, LEONE G, GIACHELIA M, et al . Analysis of genome-wide methylation and gene expression induced by 5-aza-2′-deoxycytidine identifies BCL2L10 as a frequent methylation target in acute myeloid leukemia[J ] . Leuk Lymphoma, 2010, 51(12): 2275-2284. DOI:10.3109/10428194.2010.528093.

VALENT P HORNY H P BENNETT J M Definitions and standards in the diagnosis and treatment of the myelodysplastic syndromes: Consensus statements and report from a working conference Leuk Res 2007 31 6 727 736 10.1016/j.leukres.2006.11.009 VALENT P, HORNY H P, BENNETT J M, et al . Definitions and standards in the diagnosis and treatment of the myelodysplastic syndromes: Consensus statements and report from a working conference[J ] . Leuk Res, 2007, 31(6): 727-736. DOI:10.1016/j.leukres.2006.11.009.

ARBER D A ORAZI A HASSERJIAN R The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia Blood 2016 127 20 2391 2405 10.1182/blood-2016-03-643544 ARBER D A, ORAZI A, HASSERJIAN R, et al . The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia[J ] . Blood, 2016, 127(20): 2391-2405. DOI:10.1182/blood-2016-03-643544.

SCHANZ J TüCHLER H SOLÉ F New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge J Clin Oncol 2012 30 8 820 829 10.1200/jco.2011.35.6394. SCHANZ J, TüCHLER H, SOLÉ F, et al . New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge[J ] . J Clin Oncol, 2012, 30(8): 820-829. DOI:10.1200/jco.2011.35.6394.

VOSO M T FENU S LATAGLIATA R Revised international prognostic scoring system (IPSS) predicts survival and leukemic evolution of myelodysplastic syndromes significantly better than IPSS and WHO prognostic scoring system: validation by the gruppo Romano mielodisplasie Italian regional database J Clin Oncol 2013 31 21 2671 2677 10.1200/jco.2012.48.0764 VOSO M T, FENU S, LATAGLIATA R, et al . Revised international prognostic scoring system (IPSS) predicts survival and leukemic evolution of myelodysplastic syndromes significantly better than IPSS and WHO prognostic scoring system: validation by the gruppo Romano mielodisplasie Italian regional database[J ] . J Clin Oncol, 2013, 31(21): 2671-2677. DOI:10.1200/jco.2012.48.0764.

MIKATA R FUKAI K IMAZEKI F BCL2L10 is frequently silenced by promoter hypermethylation in gastric cancer Oncol Rep 2010 23 6 1701 1708 10.3892/or_00000814 MIKATA R, FUKAI K, IMAZEKI F, et al . BCL2L10 is frequently silenced by promoter hypermethylation in gastric cancer[J ] . Oncol Rep, 2010, 23(6): 1701-1708. DOI:10.3892/or_00000814.

HE J F DENG L LIU H P BCL2L10/BECN1 modulates hepatoma cells autophagy by regulating PI3K/AKT signaling pathway Aging 2019 11 2 350 370 10.18632/aging.101737 HE J F, DENG L, LIU H P, et al . BCL2L10/BECN1 modulates hepatoma cells autophagy by regulating PI3K/AKT signaling pathway[J ] . Aging, 2019, 11(2): 350-370. DOI:10.18632/aging.101737.

NAUMANN U WEIT S WISCHHUSEN J Diva/Boo is a negative regulator of cell death in human glioma cells FEBS Lett 2001 505 1 23 26 10.1016/s0014-5793(01)02768-5 NAUMANN U, WEIT S, WISCHHUSEN J, et al . Diva/Boo is a negative regulator of cell death in human glioma cells[J ] . FEBS Lett, 2001, 505(1): 23-26. DOI:10.1016/s0014-5793(01)02768-5.

MIKATA R YOKOSUKA O FUKAI K Analysis of genes upregulated by the demethylating agent 5-aza-2′-deoxycytidine in gastric cancer cell lines Int J Cancer 2006 119 7 1616 1622 10.1002/ijc.21968 MIKATA R, YOKOSUKA O, FUKAI K, et al . Analysis of genes upregulated by the demethylating agent 5-aza-2′-deoxycytidine in gastric cancer cell lines[J ] . Int J Cancer, 2006, 119(7): 1616-1622. DOI:10.1002/ijc.21968.

VOSO M T FABIANI E PICIOCCHI A Role of BCL2L10 methylation and TET2 mutations in higher risk myelodysplastic syndromes treated with 5-azacytidine Leukemia 2011 25 12 1910 1913 10.1038/leu.2011.170 VOSO M T, FABIANI E, PICIOCCHI A, et al . Role of BCL2L10 methylation and TET2 mutations in higher risk myelodysplastic syndromes treated with 5-azacytidine[J ] . Leukemia, 2011, 25(12): 1910-1913. DOI:10.1038/leu.2011.170.

MONTALBANBRAVO G TAKAHASHI K PATEL K P Impact of the number of mutations in survival and response outcomes to hypomethylating agents in patients with myelodysplastic syndromes or myelodysplastic/myeloproliferative neoplasms Oncotarget 2018 9 11 9714 9727 10.18632/oncotarget.23882 MONTALBANBRAVO G, TAKAHASHI K, PATEL K P, et al . Impact of the number of mutations in survival and response outcomes to hypomethylating agents in patients with myelodysplastic syndromes or myelodysplastic/myeloproliferative neoplasms[J ] . Oncotarget, 2018, 9(11): 9714-9727. DOI:10.18632/oncotarget.23882.

JIANG X J WANG Z X DING B J The hypomethylating agent decitabine prior to chemotherapy improves the therapy efficacy in refractory/relapsed acute myeloid leukemia patients Oncotarget 2015 6 32 33612 33622 10.18632/oncotarget.5600 JIANG X J, WANG Z X, DING B J, et al . The hypomethylating agent decitabine prior to chemotherapy improves the therapy efficacy in refractory/relapsed acute myeloid leukemia patients[J ] . Oncotarget, 2015, 6(32): 33612-33622. DOI:10.18632/oncotarget.5600.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Correlation between H.pylori infection-increased Runx3 methylation in gastric cancer tissue and survival rate of gastric cancer patients

A novel estrogen receptor expression stratification (low/moderate/high) based on Chinese population provides more accurate prognosis prediction for HR⁺/HER2^- early breast cancer patients

Immunosuppressive microenvironment of TGIF1-overexpressing gastric cancers and its clinical significance

Impact of molecular heterogeneity of NPM1 mutations on prognosis of acute myeloid leukemia: a clinical report of 86 cases

Related Author

赵永勋

关泉林

张兴旺

赵鹏

汪晓炜

袁文臻

曹农

WU Zhenzhen

Related Institution

The First Clinical Medical College， Lanzhou University

Department of Hematology， the Second Hospital & Clinical Medical School， Lanzhou University

Department of Hematology， Gansu Provincial Hospital

Gansu Provincial Clinical Medical Research Center for Molecular Diagnosis and Treatment of Hematological Diseases， the First Hospital， Lanzhou University

The Laboratory Center， the First Hospital， Lanzhou University

⁰