Latest Findings on the Mechanism of the Interaction Between Multiple Myeloma Cells and Bone Marrow Microenvironment

HE Ni-han, ZHOU Wen

Abstract

Multiple myeloma (MM) is a hematologic malignancy of terminally differentiated plasma cells. The mechanisms of the pathogenesis and progression of MM include genetic abnormalities of the MM cells and the interaction between MM cells and bone marrow microenvironment (BMME). MM cells start malignant proliferation in BMME and contribute to the pathogenesis and progression of MM through direct or indirect interactions between cells and the extracellular matrix. Exploring the mechanism of interaction between MM cells and the microenvironment is crucial to improving our understanding of the pathogenesis and progression of MM and early diagnosis and treatment. In addition, the metabolic reprogramming of tumors is one of the key issues of oncology research. Herein, we summarized published findings on the the altered metabolic reprogramming of MM and the characteristics of MM metabolic-microbial interactions in order to gain an in-depth understanding of MM pathogenesis and progression and drug resistance mechanisms, and ultimately to explore for new strategies for MM treatment.

 

Keywords: Multiple myeloma, Clonal evolution, Bone marrow microenvironment, Metabolic microenvironment

 

Full Text:

PDF


References


LANDGREN O， HULTCRANTZ M， DIAMOND B， et al. Safety and effectiveness of weekly carfilzomib, lenalidomide, dexamethasone, and daratumumab combination therapy for patients with newly diagnosed multiple myeloma: the MANHATTAN Nonrandomized Clinical Trial. JAMA Oncol，2021，7(6): 862–868. doi: 10.1001/jamaoncol.2021.0611.

ZANG M， GUO J， LIU L， et al. Cdc37 suppression induces plasma cell immaturation and bortezomib resistance in multiple myeloma via Xbp1s. Oncogenesis，2020，9(3): 31. doi: 10.1038/s41389-020-0216-1.

WALKER B A， MAVROMMATIS K， WARDELL C P， et al. A high-risk, double-hit, group of newly diagnosed myeloma identified by genomic analysis. Leukemia，2019，33(1): 159–170. doi: 10.1038/s41375-018-0196-8.

LI N， JOHNSON D C， WEINHOLD N， et al. Multiple myeloma risk variant at 7p15.3 creates an IRF4-binding site and interferes with

CDCA7L expression. Nat Commun，2016，7: 13656. doi: 10.1038/ncomms13656.

MAURA F， BOLLI N， ANGELOPOULOS N， et al. Genomic landscape and chronological reconstruction of driver events in multiple myeloma. Nat Commun，2019，10(1): 3835. doi: 10.1038/s41467-019-11680-1.

ZHOU W， YANG Y， XIA J， et al. NEK2 induces drug resistance mainly through activation of efflux drug pumps and is associated with poor prognosis in myeloma and other cancers. Cancer Cell，2013，23(1): 48–62. doi: 10.1016/j.ccr.2012.12.001.

XIA J， HE Y， MENG B， et al. NEK2 induces autophagy-mediated bortezomib resistance by stabilizing Beclin-1 in multiple myeloma. Mol Oncol，2020，14(4): 763–778. doi: 10.1002/1878-0261.12641.

FENG X， GUO J， AN G， et al. Genetic aberrations and interaction of NEK2 and TP53 accelerate aggressiveness of multiple myeloma. Adv Sci (Weinh)，2022，9(9): e2104491. doi: 10.1002/advs.202104491.

KUMAR S K， RAJKUMAR V， KYLE R A， et al. Multiple myeloma. Nat Rev Dis Primers，2017，3: 17046. doi: 10.1038/nrdp.2017.46.

LVJ， SUN H， GONG L， et al. Aberrant metabolic processes promote the immunosuppressive microenvironment in multiple myeloma. Front Immunol，2022，13: 1077768. doi: 10.3389/fimmu.2022.1077768.

KAWANO Y， ZAVIDIJ O， PARK J， et al. Blocking IFNAR1 inhibits multiple myeloma-driven Treg expansion and immunosuppression. J Clin Invest，2018，128(6): 2487–2499. doi: 10.1172/JCI88169.

YANG Q， LI X， ZHANG F， et al. Efficacy and Safety of CAR-T therapy for relapse or refractory multiple myeloma: a systematic review and meta-analysis. Int J Med Sci，2021，18(8): 1786–1797. doi: 10.7150/ijms.46811.

MANIER S， SALEM KZ， PARK J， et al. Genomic complexity of multiple myeloma and its clinical implications. Nat Rev Clin Oncol，2017，14(2): 100–113. doi: 10.1038/nrclinonc.2016.122.

NAKAMURA K， KASSEM S， CLEYNEN A， et al. Dysregulated IL-18 is a key driver of immunosuppression and a possible therapeutic target in the multiple myeloma microenvironment. Cancer Cell，2018，33(4): 634–648.e5. doi: 10.1016/j.ccell.2018.02.007.

NATONI A， FARRELL M L， HARRIS S， et al. Sialyltransferase inhibition leads to inhibition of tumor cell interactions with E-selectin, VCAM1, and MADCAM1, and improves survival in a human multiple myeloma mouse model. Haematologica，2020，105(2): 457–467. doi: 10. 3324/haematol.2018.212266.

KUANG C， ZHU Y， GUAN Y， et al. COX2 confers bone marrow stromal cells to promoting TNFα/TNFR1β-mediated myeloma cell growth and adhesion. Cell Oncol (Dordr)，2021，44(3): 643–659. doi: 10. 1007/s13402-021-00590-4.

GAU Y C， YEH T J， HSU C M， et al. Pathogenesis and treatment of myeloma-related bone disease. Int J Mol Sci，2022，23(6): 3112. doi: 10. 3390/ijms23063112.

FAIRFIELD H， DUDAKOVIC A， KHATIB C M， et al. Myeloma-modified adipocytes exhibit metabolic dysfunction and a senescence- associated secretory phenotype. Cancer Res，2021，81(3): 634–647. doi: 10. 1158/0008-5472.CAN-20-1088.

HIDESHIMA T， CATLEY L， YASUI H， et al. Perifosine, an oral bioactive novel alkylphospholipid, inhibits Akt and induces in vitro and in vivo cytotoxicity in human multiple myeloma cells. Blood，2006， 107(10): 4053–4062. doi: 10.1182/blood-2005-08-3434.

HIDESHIMA T， CHAUHAN D， SCHLOSSMAN R， et al. The role of tumor necrosis factor alpha in the pathophysiology of human multiple myeloma: therapeutic applications. Oncogene，2001，20(33): 4519–4527. doi: 10.1038/sj.onc.1204623.

WENTHE J， NASERI S， HELLSTROM A C， et al. Immunostimulatory oncolytic virotherapy for multiple myeloma targeting 4-1BB and/or CD40. Cancer Gene Ther，2020，27(12): 948–959. doi: 10.1038/s41417-020-0176-9.

SALTARELLA I， MORABITO F， GIULIANI N， et al. Prognostic or predictive value of circulating cytokines and angiogenic factors for initial treatment of multiple myeloma in the GIMEMA MM0305 randomized controlled trial. J Hematol Oncol，2019，12(1): 4. doi: 10.1186/s13045-018-0691-4.

TERPOS E， ANARGYROU K， KATODRITOU E， et al. Circulating angiopoietin-1 to angiopoietin-2 ratio is an independent prognostic factor for survival in newly diagnosed patients with multiple myeloma who received therapy with novel antimyeloma agents. Int J Cancer，2012， 130(3): 735–742. doi: 10.1002/ijc.26062.

VACC A， RIBATTI D， PRESTA M， et al. Bone marrow neovascularization, plasma cell angiogenic potential, and matrix metalloproteinase-2 secretion parallel progression of human multiple myeloma. Blood，1999，93(9): 3064–3073. doi: 10.1182/blood.V93.9.3064. 409k07_3064_3073.

MURPHY-ULLRICH J E， SUTO M J. Thrombospondin-1 regulation of latent TGF-β activation: a therapeutic target for fibrotic disease. Matrix Biol，2018，68-69: 28–43. doi: 10.1016/j.matbio.2017.12.009.

LACINA P， BUTRYM A， HUMMINSKI M， et al. Association of RANK and RANKL gene polymorphism with survival and calcium levels in multiple myeloma. Mol Carcinog，2021，60(2): 106–112. doi: 10.1002/mc. 23272.

SPATH F， WIBOM C， KROP E J M， et al. Immune marker changes and risk of multiple myeloma: a nested case-control study using repeated pre-diagnostic blood samples. Haematologica，2019，104(12): 2456–2464. doi: 10.3324/haematol.2019.216895.

LI X， WANG J， ZHU S， et al. DKK1 activates noncanonical NF-κB signaling via IL-6-induced CKAP4 receptor in multiple myeloma. Blood Adv，2021，5(18): 3656–3667. doi: 10.1182/bloodadvances.2021004315.

EVANS L A， ANDERSON E A， JESSEN E， et al. Overexpression of the energy metabolism transcriptome within clonal plasma cells is associated with the pathogenesis and outcomes of patients with multiple myeloma. Am J Hematol，2022，97(7): 895–902. doi: 10.1002/ajh.26577.


Refbacks

  • There are currently no refbacks.