JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B

Accepted manuscript available online (unedited version)

High levels of serum IL-10 indicate disease progression, extramedullary involvement, and poor prognosis in multiple myeloma

Author(s): Xiaoyan YUE, Linlin HUANG, Yang YANG, Yi ZHAO, Donghua HE, Xiaoyan HAN, Gaofeng ZHENG, Yi LI, Enfan ZHANG, Zhen CAI, Xin HUANG, Jingsong HE
Affiliation(s): Bone Marrow Transplantation Center, Department of Hematology, the First Affiliated Hospital, School of Medicine, Zhejiang University,Hangzhou310003,China; more
Corresponding email(s): hejingsong@zju.edu.cn
Key Words: Multiple myeloma, Interleukin-10, Extramedullary multiple myeloma, PFS, OS

Share this article to： More <<< Previous Paper \|

Xiaoyan YUE, Linlin HUANG, Yang YANG, Yi ZHAO, Donghua HE, Xiaoyan HAN, Gaofeng ZHENG, Yi LI, Enfan ZHANG, Zhen CAI, Xin HUANG, Jingsong HE. High levels of serum IL-10 indicate disease progression, extramedullary involvement, and poor prognosis in multiple myeloma[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2200277

@article{title="High levels of serum IL-10 indicate disease progression, extramedullary involvement, and poor prognosis in multiple myeloma",
author="Xiaoyan YUE, Linlin HUANG, Yang YANG, Yi ZHAO, Donghua HE, Xiaoyan HAN, Gaofeng ZHENG, Yi LI, Enfan ZHANG, Zhen CAI, Xin HUANG, Jingsong HE",
journal="Journal of Zhejiang University Science B",
year="in press",
publisher="Zhejiang University Press & Springer",
doi="https://doi.org/10.1631/jzus.B2200277"
}

%0 Journal Article
%T High levels of serum IL-10 indicate disease progression, extramedullary involvement, and poor prognosis in multiple myeloma
%A Xiaoyan YUE
%A Linlin HUANG
%A Yang YANG
%A Yi ZHAO
%A Donghua HE
%A Xiaoyan HAN
%A Gaofeng ZHENG
%A Yi LI
%A Enfan ZHANG
%A Zhen CAI
%A Xin HUANG
%A Jingsong HE
%J Journal of Zhejiang University SCIENCE B
%P 968-974
%@ 1673-1581
%D in press
%I Zhejiang University Press & Springer
doi="https://doi.org/10.1631/jzus.B2200277"

TY - JOUR
T1 - High levels of serum IL-10 indicate disease progression, extramedullary involvement, and poor prognosis in multiple myeloma
A1 - Xiaoyan YUE
A1 - Linlin HUANG
A1 - Yang YANG
A1 - Yi ZHAO
A1 - Donghua HE
A1 - Xiaoyan HAN
A1 - Gaofeng ZHENG
A1 - Yi LI
A1 - Enfan ZHANG
A1 - Zhen CAI
A1 - Xin HUANG
A1 - Jingsong HE
J0 - Journal of Zhejiang University Science B
SP - 968
EP - 974
%@ 1673-1581
Y1 - in press
PB - Zhejiang University Press & Springer
ER -
doi="https://doi.org/10.1631/jzus.B2200277"

Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: multiple myeloma (MM) is a common malignant hematological tumor in adults, which is characterized by clonal malignant proliferation of plasma cells in the bone marrow and secretion of a large number of abnormal monoclonal immunoglobulins (M protein), leading to bone destruction, hypercalcemia, anemia, and renal insufficiency (Alexandrakis et al., 2015; Yang et al., 2018). Since a large number of new drugs, represented by proteasome inhibitors and immunomodulators, have been successfully used to treat MM, treatment efficacy and survival of patients have been significantly improved. However, due to the high heterogeneity of this disease, patients have responded differently to treatments with these new drugs (Palumbo and Anderson, 2011; Wang et al., 2016; Huang et al., 2020). Growth and survival of MM cells depend on the bone marrow microenvironment, especially numerous inflammatory cytokines secreted by myeloma cells and bone marrow stromal cells, such as vascular endothelial growth factor (VEGF), interleukin (IL)‍-6, transforming growth factor-‍β (TGF‍‍-‍‍β), and IL-10. These cytokines can promote the growth of myeloma cells, induce angiogenesis, and inhibit antitumor immunity, and are often linked to patient prognOSis (Kumar et al., 2017). In this era of new drugs, the prognOStic values of the serum levels of these cytokines in MM need further evaluation.

血清高水平白细胞介素-10提示多发性骨髓瘤患者疾病进展、髓外累及和不良预后

岳小艳¹，黄琳琳¹，杨杨¹，赵毅¹，何冬花¹，韩晓雁¹，郑高锋¹，李奕¹，张恩帆¹，蔡真^1,2,3，黄昕⁴，何静松¹
¹浙江大学医学院附属第一医院血液科＆骨髓移植中心，中国杭州，310003
²浙江大学血液学研究所，中国杭州，310058
³浙江大学医学中心，浙江省系统&精准医学实验室，中国杭州，311121
⁴浙江大学医学院附属第一医院血液科&血液学研究所，中国杭州，310003
概要：多发性骨髓瘤（MM）细胞的生长和存活依赖于骨髓微环境，其中细胞因子常与疾病的不良预后有关。在新药治疗时代，血清细胞因子水平对MM预后作用需进一步评估。本研究分析了157例初诊MM患者外周血细胞因子水平（包括白细胞介素-2（IL-2）、IL-4、IL-6、IL-10、干扰素γ（IFN-γ）、肿瘤坏死因子α（TNF-α）和IL-17A）与患者基线临床特征、疗效以及预后之间的关系。并选用15例年龄契合的健康志愿者和96例复发MM患者作为对照。所有患者均一线接受硼替佐米为基础方案的治疗。生存分析表明，上述细胞因子中，仅血清IL-10与患者的无进展生存期（PFS）和总生存期（OS）显著相关。初诊MM患者中，有103例（65.6%）患者被归为高IL-10（≥1.42 pg/mL）组，该组患者通常具有高危基因异常和临床分期，也更容易出现贫血、血小板减少，以及血清乳酸脱氢酶、C-反应蛋白和肌酐水平增高的症状。单因素分析表明高IL-10组患者有更差的PFS（P＝0.040）和OS（P<0.001），多因素分析提示血清IL-10是初诊MM患者OS的独立预后因素。研究结果提示，血清IL-10水平与MM患者疾病进展和高危临床特征相关，可作为以硼替佐米为基础治疗方案的初诊MM患者OS的预后因素。

关键词组：多发性骨髓瘤；白细胞介素-10；临床特征；无进展生存期；总生存期

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]AlexandrakisMG,GoulidakiN,PappaCA,et al.,2015.Interleukin-10 induces both plasma cell proliferation and angiogenesis in multiple myeloma.Pathol Oncol Res,21(4):929-934.

[2]FayadL,KeatingMJ,ReubenJM,et al.,2001.Interleukin-6 and interleukin-10 levels in chronic lymphocytic leukemia: correlation with phenotypic characteristics and outcome.Blood,97(1):256-263.

[3]GuptaM,HanJJ,StensonM,et al.,2012.Elevated serum IL-10 levels in diffuse large B-cell lymphoma: a mechanism of aberrant JAK2 activation.Blood,119(12):‍2844-2853.

[4]HeJS,HeDH,HanXY,et al.,2020.Bortezomib-based regimens for newly diagnosed multiple myeloma in China: a report of 12-year real-world data.Front Pharmacol,11:561601.

[5]HeJS,YueXY,HeDH,et al.,2021.Multiple extramedullary-bone related and/or extramedullary extraosseous are independent poor prognostic factors in patients with newly diagnosed multiple myeloma.Front Oncol,11:668099.

[6]HuangH,WuHW,HuYX,et al.,2020.Current advances in chimeric antigen receptor T-cell therapy for refractory/relapsed multiple myeloma.J Zhejiang Univ-Sci B (Biomed & Biotechnol), 2020,21(1):29-41.

[7]KumarSK,RajkumarV,KyleRA,et al.,2017.Multiple myeloma.Nat Rev Dis Primers,3:17046.

[8]MinnieSA,KunsRD,GartlanKH,et al.,2018.Myeloma escape after stem cell transplantation is a consequence of T-cell exhaustion and is prevented by TIGIT blockade.Blood,132(16):1675-1688.

[9]MusolinoC,AllegraA,InnaoV,et al.,2017.Inflammatory and anti-inflammatory equilibrium, proliferative and antiproliferative balance: the role of cytokines in multiple myeloma.Mediators Inflamm,2017:1852517.

[10]Načinović-DuletićA,ŠtifterS,DvornikŠ,et al.,2008.Correlation of serum IL-6, IL-8 and IL-10 levels with clinicopathological features and prognosis in patients with diffuse large B-cell lymphoma.Int J Lab Hematol,30(3):230-239.

[11]PalumboA,AndersonK,2011.Multiple myeloma.N Engl J Med,364(11):1046-1060.

[12]RajkumarSV,DimopoulosMA,PalumboA,et al.,2014.International myeloma working group updated criteria for the diagnosis of multiple myeloma.Lancet Oncol,15(12):e538-e548.

[13]RyuD,KimSJ,HongY,et al.,2020.Alterations in the transcriptional programs of myeloma cells and the microenvironment during extramedullary progression affect proliferation and immune evasion.Clin Cancer Res,26(4):935-944.

[14]ShekarrizR,JanbabaeiG,KenariSA,2018.Prognostic value of IL-10 and its relationship with disease stage in Iranian patients with multiple myeloma.Asian Pac J Cancer Prev,19(1):27-32.

[15]WangH,WangL,ChiPD,et al.,2016.High level of interleukin-10 in serum predicts poor prognosis in multiple myeloma.Br J Cancer,114(4):463-468.

[16]YangRN,ChangQ,MengXC,et al.,2018.Prognostic value of systemic immune-inflammation index in cancer: a meta-analysis.J Cancer,9(18):3295-3302.

Open peer comments: Debate/Discuss/Question/Opinion

<1>

- Go to

血清高水平白细胞介素-10提示多发性骨髓瘤患者疾病进展、髓外累及和不良预后

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference