|Table of Contents|

Current status of research on the mechanism of drug resistance of bone marrow microenvironment-mediated proteasome inhibitors in the treatment of multiple myeloma

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 22
Page:
4289-4294
Research Field:
Publishing date:

Info

Title:
Current status of research on the mechanism of drug resistance of bone marrow microenvironment-mediated proteasome inhibitors in the treatment of multiple myeloma
Author(s):
WU Min; LI Yinghua
Hematology Department,the First Affiliated Hospital of Harbin Medical University，Heilongjiang Harbin 150000,China.
Keywords:
multiple myeloma; bone marrow microenvironment; proteasome inhibitors; drug resistance; bortezomib
PACS:
R733.3
DOI:
10.3969/j.issn.1672-4992.2023.22.037
Abstract:
Multiple myeloma (MM) is a plasma cell proliferative malignant disease.In recent years,with the introduction of new drugs such as proteasome inhibitor (PI),immunomodulator,CD38 monoclonal antibody and the development of autologous stem cell transplantation,some progress has been made in the treatment of MM patients,but MM is still an incurable malignant tumor.The main cause of disease progression and death is drug resistance of MM cells,so we need new therapy urgently.The bone marrow microenvironment is regarded as the "soil" of hematopoietic stem cells,and its characteristic three-dimensional structure provides the basis for the survival of hematopoietic stem cells.It is closely related to the regulation of hematopoietic production,stem cell mobilization and homing and other life activities.The intricate relationship between MM cells and the bone marrow microenvironment affects the proliferation,survival and drug resistance of MM cells.This article mainly focuses on MM,bone marrow microenvironment and the mechanism of patients' resistance to related proteasome inhibitors,in order to find a new combination treatment plan to overcome bortezomib resistance and improve the prognosis of patients.

References:

［1］ SAKI N,ABROUN S,HAJIZAMANI S,et al.Association of chromosomal translocation and miRNA expression with the pathogenesis of multiple myeloma［J］.Cell J,2014,16(2):99-110.
［2］ LIU J,LIU W,MI L,et al.Incidence and mortality of multiple myeloma in China,2006-2016:an analysis of the global burden of disease study 2016［J］.J Hematol Oncol,2019,12(1):136.
［3］ ZHANG J,YE Z,CHEN W,et al.Altered redox regulation and S-glutathionylation of BiP contribute to bortezomib resistance in multiple myeloma［J］.Free Radical Biology and Medicine,2020,160:755-767.
［4］ ZHENG Y,YANG J,QIAN J,et al.PSGL-1/selectin and ICAM-1/CD18 interactions are involved in macrophage-induced drug resistance in myeloma［J］.Leukemia,2013,27(3):702-710.
［5］ TANG JX,CHEN Q,LI Q,et al.Exosomal mRNAs and lncRNAs involved in multiple myeloma resistance to bortezomib［J］.Cell Biol Int,2021,45(5):965-975.
［6］ GARCIA-ORTIZ A,RODRIGUEZ-GARCIA Y,ENCINAS J,et al.The role of tumor microenvironment in multiple myeloma development and progression［J］.Cancers (Basel),2021,13(2):217.
［7］ MURRAY MY,AUGER MJ,BOWLES KM.Overcoming bortezomib resistance in multiple myeloma［J］.Biochem Soc Trans,2014,42(4):804-808.
［8］ HEINE A,HELD S,SCHULTE-SCHREPPING J,et al.Generation and functional characterization of MDSC-like cells［J］.Oncoimmunology,2017,6(4):e1295203.
［9］ GORGUN GT,WHITEHILL G,ANDERSON JL,et al.Tumor-promoting immune-suppressive myeloid-derived suppressor cells in the multiple myeloma microenvironment in humans［J］.Blood,2013,121(15):2975-2987.
［10］ SOLITO S,FALISI E,DIAZ-MONTERO CM,et al.A human promyelocytic-like population is responsible for the immune suppression mediated by myeloid-derived suppressor cells［J］.Blood,2011,118(8):2254-2265.
［11］ WANG H,HU WM,XIA ZJ,et al.High numbers of CD163+ tumor-associated macrophages correlate with poor prognosis in multiple myeloma patients receiving bortezomib-based regimens［J］.J Cancer,2019,10(14):3239-3245.
［12］ MUKHERJEE S,RAJE N,SCHOONMAKER JA,et al.Pharmacologic targeting of a stem/progenitor population in vivo is associated with enhanced bone regeneration in mice［J］.J Clin Invest,2008,118(2):491-504.
［13］ YU SJ,MA C,HEINRICH B,et al.Targeting the crosstalk between cytokine-induced killer cells and myeloid-derived suppressor cells in hepatocellular carcinoma［J］.J Hepatol,2019,70(3):449-457.
［14］ WEED DT,VELLA JL,REIS IM,et al.Tadalafil reduces myeloid-derived suppressor cells and regulatory T cells and promotes tumor immunity in patients with head and neck squamous cell carcinoma［J］.Clin Cancer Res,2015,21(1):39-48.
［15］ NOONAN KA,GHOSH N,RUDRARAJU L,et al.Targeting immune suppression with PDE5 inhibition in end-stage multiple myeloma［J］.Cancer Immunol Res,2014,2(8):725-731.
［16］ BRIMNES MK,VANGSTED AJ,KNUDSEN LM,et al.Increased level of both CD4+FOXP3+ regulatory T cells and CD14+HLA-DR(-)/low myeloid-derived suppressor cells and decreased level of dendritic cells in patients with multiple myeloma［J］.Scand J Immunol,2010,72(6):540-547.
［17］ GIANNOPOULOS K,KAMINSKA W,HUS I,et al.The frequency of T regulatory cells modulates the survival of multiple myeloma patients:detailed characterisation of immune status in multiple myeloma［J］.Br J Cancer,2012,106(3):546-552.
［18］ CHUNG DJ,PRONSCHINSKE KB,SHYER JA,et al.T-cell exhaustion in multiple myeloma relapse after autotransplant:optimal timing of immunotherapy［J］.Cancer Immunol Res,2016,4(1):61-71.
［19］ HADJIAGGELIDOU C,MANDALA E,TERPOS E,et al.Evaluation of regulatory T cells (Tregs) alterations in patients with multiple myeloma treated with bortezomib or lenalidomide plus dexamethasone:correlations with treatment outcome［J］.Ann Hematol,2019,98(6):1457-1466.
［20］ MUTHU RK,KOVAROVA L,HAJEK R.Induction by lenalidomide and dexamethasone combination increases regulatory cells of patients with previously untreated multiple myeloma［J］.Leuk Lymphoma,2012,53(7):1406-1408.
［21］ ERCETIN AP,OZCAN MA,AKTAS S,et al.Ex vivo evaluation of the effect of regulatory T cells on the anti-tumor activity of bortezomib in multiple myeloma［J］.Exp Hematol,2016,44(4):223-230.
［22］ WANG X,HE Y,TIAN S,et al.Fluid shear stress increases osteocyte and inhibits osteoclasts via downregulating receptor-activator of nuclear factor kappaB (RANK)/osteoprotegerin expression in myeloma microenvironment［J］.Med Sci Monit,2019,25:5961-5968.
［23］ CROCKETT JC,ROGERS MJ,COXON FP,et al.Bone remodelling at a glance［J］.J Cell Sci,2011,124(Pt7):991-998.
［24］ TAI YT,CHO SF,ANDERSON KC.Osteoclast immunosuppressive effects in multiple myeloma:role of programmed cell death ligand 1［J］.Front Immunol,2018,9:1822.
［25］ ABELTINO M,BONOMINI S,BOLZONI M,et al.The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide［J］.Exp Hematol,2011,39(1):55-65.
［26］ MARTINEZ-MORENO M,LEIVA M,AGUILERA-MONTILLA N,et al.In vivo adhesion of malignant B cells to bone marrow microvasculature is regulated by alpha4beta1 cytoplasmic-binding proteins［J］.Leukemia,2016,30(4):861-872.
［27］ REDONDO-MUNOZ J,GARCIA-PARDO A,TEIXIDO J.Molecular players in hematologic tumor cell trafficking［J］.Front Immunol,2019,10:156.
［28］ SEVILLA MOVILLA S,ARELLANO SANCHEZ N,MARTINEZ MORENO M,et al.Upregulated expression and function of the α4β1 integrin in multiple myeloma cells resistant to bortezomib［J］.The Journal of Pathology,2020,252(1):29-40.
［29］ MORI Y,SHIMIZU N,DALLAS M,et al.Anti-alpha4 integrin antibody suppresses the development of multiple myeloma and associated osteoclastic osteolysis［J］.Blood,2004,104(7):2149-2154.
［30］ OLSON DL,BURKLY LC,LEONE DR,et al.Anti-alpha4 integrin monoclonal antibody inhibits multiple myeloma growth in a murine model［J］.Mol Cancer Ther,2005,4(1):91-99.
［31］ PLATONOVA N,LESMA E,BASILE A,et al.Targeting Notch as a therapeutic approach for human malignancies［J］.Curr Pharm Des,2017,23(1):108-134.
［32］ COLOMBO M,MIRANDOLA L,CHIRIVA-INTERNATI M,et al.Cancer cells exploit notch signaling to redefine a supportive cytokine milieu［J］.Front Immunol,2018,9:1823.
［33］ SALTARELLA I,FRASSANITO MA,LAMANUZZI A,et al.Homotypic and heterotypic activation of the notch pathway in multiple myeloma-enhanced angiogenesis:a novel therapeutic target［J］.Neoplasia,2019,21(1):93-105.
［34］ COLOMBO M,GALLETTI S,BULFAMANTE G,et al.Multiple myeloma-derived Jagged ligands increases autocrine and paracrine interleukin-6 expression in bone marrow niche［J］.Oncotarget,2016,7(35):56013-56029.
［35］ HOUDE C,LI Y,SONG L,et al.Overexpression of the NOTCH ligand JAG2 in malignant plasma cells from multiple myeloma patients and cell lines［J］.Blood,2004,104(12):3697-3704.
［36］ MUGURUMA Y,YAHATA T,WARITA T,et al.Jagged1-induced Notch activation contributes to the acquisition of bortezomib resistance in myeloma cells［J］.Blood Cancer J,2017,7(12):650.
［37］ XU D,HU J,DE BRUYNE E,et al.Dll1/Notch activation contributes to bortezomib resistance by upregulating CYP1A1 in multiple myeloma［J］.Biochem Biophys Res Commun,2012,428(4):518-524.
［38］ JOHNSON DE,O'KEEFE RA,GRANDIS JR.Targeting the IL-6/JAK/STAT3 signalling axis in cancer［J］.Nat Rev Clin Oncol,2018,15(4):234-248.
［39］ 沈静,张永超,杨融辉,等.血清IL-6及IL-10在非霍奇金淋巴瘤患者血清中的表达及临床意义［J］.现代肿瘤医学，2022,30(06):1076－1079. SHEN Jing,ZHANG Yongchao,YANG Ronghui,et al.Expression and clinical significance of serum IL-6 and IL-10 in patients with non-Hodgkin' s lymphoma［J］.Modern Oncology,2022,30(06):1076－1079.
［40］ 袁琪,王伟,徐春华.晚期非小细胞肺癌恶性胸腔积液IL-6水平与EGFR-TKIs治疗疗效及预后的关系［J］.现代肿瘤医学，2022,30(07):1224-1228. YUAN Qi,WANG Wei,XU Chunhua.Pleural IL-6 level predicts clinical outcomes in patients with advanced non-small cell lung cancer receiving EGFR-TKIs［J］.Modern Oncology,2022,30(07):1224-1228.
［41］ KOERBER RM,HELD S,HEINE A,et al.Analysis of the anti-proliferative and the pro-apoptotic efficacy of Syk inhibition in multiple myeloma［J］.Exp Hematol Oncol,2015,4:21.
［42］ HARMER D,FALANK C,REAGAN MR.Interleukin-6 interweaves the bone marrow microenvironment,bone loss,and multiple myeloma［J］.Frontiers in Endocrinology,2019,9:788.
［43］ YOSIFOV DY,REUFSTECK C,KONSTANTINOV SM,et al.Interleukin-6,osteopontin and Raf/MEK/ERK signaling modulate the sensitivity of human myeloma cells to alkylphosphocholines［J］.Leuk Res,2012,36(6):764-772.
［44］ PEIXOTO DA SILVA S,CAIRES HR,BERGANTIM R,et al.miRNAs mediated drug resistance in hematological malignancies［J］.Seminars in Cancer Biology,2022,83:283-302.
［45］ ORLOWSKI R Z,GERCHEVA L,WILLIAMS C,et al.A phase 2,randomized,double-blind,placebo-controlled study of siltuximab (anti-IL-6 mAb) and bortezomib versus bortezomib alone in patients with relapsed or refractory multiple myeloma［J］.Am J Hematol,2015,90(1):42-49.
［46］ XIANG RF,WANG Y,ZHANG N,et al.MK2206 enhances the cytocidal effects of bufalin in multiple myeloma by inhibiting the AKT/mTOR pathway［J］.Cell Death Dis,2017,8(5):e2776.
［47］ VOORHEES PM,CHEN Q,SMALL GW,et al.Targeted inhibition of interleukin-6 with CNTO 328 sensitizes pre-clinical models of multiple myeloma to dexamethasone-mediated cell death［J］.Br J Haematol,2009,145(4):481-490.
［48］ VOORHEES PM,CHEN Q,KUHN DJ,et al.Inhibition of interleukin-6 signaling with CNTO 328 enhances the activity of bortezomib in preclinical models of multiple myeloma［J］.Clin Cancer Res,2007,13(21):6469-6478.
［49］ WAUGH DJ,WILSON C.The interleukin-8 pathway in cancer［J］.Clin Cancer Res,2008,14(21):6735-6741.
［50］ PELLEGRINO A,RIA R,DI PIETRO G,et al.Bone marrow endothelial cells in multiple myeloma secrete CXC-chemokines that mediate interactions with plasma cells［J］.Br J Haematol,2005,129(2):248-256.
［51］ ROBAK P,WEGLOWSKA E,DROZDZ I,et al.Cytokine and chemokine profile in patients with multiple myeloma treated with bortezomib［J］.Mediators Inflamm,2020,2020:1835836.
［52］ HERRERO AB,GARCIA-GOMEZ A,GARAYOA M,et al.Effects of IL-8 up-regulation on cell survival and osteoclastogenesis in multiple myeloma［J］.The American Journal of Pathology,2016,186(8):2171-2182.
［53］ GU JL,LI J,ZHOU ZH,et al.Differentiation induction enhances bortezomib efficacy and overcomes drug resistance in multiple myeloma［J］.Biochem Biophys Res Commun,2012,420(3):644-650.
［54］ MARKOVINA S,CALLANDER NS,O'CONNOR SL,et al.Bone marrow stromal cells from multiple myeloma patients uniquely induce bortezomib resistant NF-kappaB activity in myeloma cells［J］.Mol Cancer,2010,9:176.
［55］ NI H,ZHAO W,KONG X,et al.NF-kappa B modulation is involved in celastrol induced human multiple myeloma cell apoptosis［J］.PLoS One,2014,9(4):e95846.
［56］ TSUYAMA N,ISHIKAWA H,ABROUN S,et al.The regulatory mechanism of IL-6-dependent proliferation of human myeloma cells［J］.Hematology,2003,8(6):409-411.
［57］ KUHN DJ,BERKOVA Z,JONES RJ,et al.Targeting the insulin-like growth factor-1 receptor to overcome bortezomib resistance in preclinical models of multiple myeloma［J］.Blood,2012,120(16):3260-3270.
［58］ KOWAL J,ARRAS G,COLOMBO M,et al.Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes［J］.Proc Natl Acad Sci USA,2016,113(8):E968-E977.
［59］ DE VEIRMAN K,WANG J,XU S,et al.Induction of miR-146a by multiple myeloma cells in mesenchymal stromal cells stimulates their pro-tumoral activity［J］.Cancer Lett,2016,377(1):17-24.
［60］ WANG J,DE VEIRMAN K,FAICT S,et al.Multiple myeloma exosomes establish a favourable bone marrow microenvironment with enhanced angiogenesis and immunosuppression［J］.J Pathol,2016,239(2):162-173.
［61］ WANG J,HENDRIX A,HERNOT S,et al.Bone marrow stromal cell-derived exosomes as communicators in drug resistance in multiple myeloma cells［J］.Blood,2014,124(4):555-566.
［62］ WANG Z,HE J,BACH DH,et al.Induction of m(6)A methylation in adipocyte exosomal LncRNAs mediates myeloma drug resistance［J］.J Exp Clin Cancer Res,2022,41(1):4.
［63］ FAICT S,MULLER J,DE VEIRMAN K,et al.Exosomes play a role in multiple myeloma bone disease and tumor development by targeting osteoclasts and osteoblasts［J］.Blood Cancer Journal (New York),2018,8(11):105-112.
［64］ GUO J,LV Y,WANG S,et al.Hypoxia induces chemoresistance to proteasome inhibitors through orchestrating deSUMOylation and ubiquitination of SRC-3 in multiple myeloma［J］.Oncogene,2022,41(45):4971-4979.
［65］ MUZ B,DE LA PUENTE P,AZAB F,et al.Hypoxia promotes stem cell-like phenotype in multiple myeloma cells［J］.Blood Cancer J,2014,4:e262.
［66］ RANINGA PV,DI TRAPANI G,VUCKOVIC S,et al.TrxR1 inhibition overcomes both hypoxia-induced and acquired bortezomib resistance in multiple myeloma through NF-small ka,Cyrillicbeta inhibition［J］.Cell Cycle,2016,15(4):559-572.
［67］ IKEDA S,ABE F,MATSUDA Y,et al.Hypoxia-inducible hexokinase-2 enhances anti-apoptotic function via activating autophagy in multiple myeloma［J］.Cancer Sci,2020,111(11):4099-4101.
［68］ CHEN HY,REN XY,WANG WH,et al.Upregulated ROS production induced by the proteasome inhibitor MG-132 on XBP1 gene expression and cell apoptosis in Tca-8113 cells［J］.Biomed Pharmacother,2014,68(6):709-713.
［69］ MUZ B,AZAB F,DE LA PUENTE P,et al.Selinexor overcomes hypoxia-induced drug resistance in multiple myeloma［J］.Transl Oncol,2017,10(4):632-640.
［70］CHARI A,VOGL DT,GAVRIATOPOULOU M,et al.Oral selinexor-dexamethasone for triple-class refractory multiple myeloma［J］.N Engl J Med,2019,381(8):727-738.

Memo

Memo:
-
Last Update: 1900-01-01