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Review

Pathways of Angiogenic and Inflammatory Cytokines in Multiple Myeloma: Role in Plasma Cell Clonal Expansion and Drug Resistance

by
Assunta Melaccio
1,*,
Antonia Reale
2,
Ilaria Saltarella
3,
Vanessa Desantis
3,
Aurelia Lamanuzzi
1,
Sebastiano Cicco
1,
Maria Antonia Frassanito
4,
Angelo Vacca
1 and
Roberto Ria
1,*
1
Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine “G. Baccelli”, University of Bari Medical School, 70124 Bari, Italy
2
Myeloma Research Group, Australian Centre for Blood Diseases, Central Clinical School, Monash University—Alfred Health, Melbourne 3004, Australia
3
Department of Biomedical Sciences and Human Oncology, Pharmacology Section, University of Bari Aldo Moro Medical School, 70124 Bari, Italy
4
General Pathology Unit, Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, 70124 Bari, Italy
*
Authors to whom correspondence should be addressed.
J. Clin. Med. 2022, 11(21), 6491; https://doi.org/10.3390/jcm11216491
Submission received: 9 October 2022 / Revised: 23 October 2022 / Accepted: 25 October 2022 / Published: 1 November 2022
(This article belongs to the Special Issue Immune Microenvironment in Solid and Hematological Malignancies)
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Abstract

Multiple myeloma (MM) is the second most common hematological malignancy, and despite the introduction of innovative therapies, remains an incurable disease. Identifying early and minimally or non-invasive biomarkers for predicting clinical outcomes and therapeutic responses is an active field of investigation. Malignant plasma cells (PCs) reside in the bone marrow (BM) microenvironment (BMME) which comprises cells (e.g., tumour, immune, stromal cells), components of the extracellular matrix (ECM) and vesicular and non-vesicular (soluble) molecules, all factors that support PCs’ survival and proliferation. The interaction between PCs and BM stromal cells (BMSCs), a hallmark of MM progression, is based not only on intercellular interactions but also on autocrine and paracrine circuits mediated by soluble or vesicular components. In fact, PCs and BMSCs secrete various cytokines, including angiogenic cytokines, essential for the formation of specialized niches called “osteoblastic and vascular niches”, thus supporting neovascularization and bone disease, vital processes that modulate the pathophysiological PCs–BMME interactions, and ultimately promoting disease progression. Here, we aim to discuss the roles of cytokines and growth factors in pathogenetic pathways in MM and as prognostic and predictive biomarkers. We also discuss the potential of targeted drugs that simultaneously block PCs’ proliferation and survival, PCs–BMSCs interactions and BMSCs activity, which may represent the future goal of MM therapy.
Keywords: multiple myeloma; angiogenic cytokines; angiogenic mimicry; osteoblastic niche; vascular niche multiple myeloma; angiogenic cytokines; angiogenic mimicry; osteoblastic niche; vascular niche

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MDPI and ACS Style

Melaccio, A.; Reale, A.; Saltarella, I.; Desantis, V.; Lamanuzzi, A.; Cicco, S.; Frassanito, M.A.; Vacca, A.; Ria, R. Pathways of Angiogenic and Inflammatory Cytokines in Multiple Myeloma: Role in Plasma Cell Clonal Expansion and Drug Resistance. J. Clin. Med. 2022, 11, 6491. https://doi.org/10.3390/jcm11216491

AMA Style

Melaccio A, Reale A, Saltarella I, Desantis V, Lamanuzzi A, Cicco S, Frassanito MA, Vacca A, Ria R. Pathways of Angiogenic and Inflammatory Cytokines in Multiple Myeloma: Role in Plasma Cell Clonal Expansion and Drug Resistance. Journal of Clinical Medicine. 2022; 11(21):6491. https://doi.org/10.3390/jcm11216491

Chicago/Turabian Style

Melaccio, Assunta, Antonia Reale, Ilaria Saltarella, Vanessa Desantis, Aurelia Lamanuzzi, Sebastiano Cicco, Maria Antonia Frassanito, Angelo Vacca, and Roberto Ria. 2022. "Pathways of Angiogenic and Inflammatory Cytokines in Multiple Myeloma: Role in Plasma Cell Clonal Expansion and Drug Resistance" Journal of Clinical Medicine 11, no. 21: 6491. https://doi.org/10.3390/jcm11216491

APA Style

Melaccio, A., Reale, A., Saltarella, I., Desantis, V., Lamanuzzi, A., Cicco, S., Frassanito, M. A., Vacca, A., & Ria, R. (2022). Pathways of Angiogenic and Inflammatory Cytokines in Multiple Myeloma: Role in Plasma Cell Clonal Expansion and Drug Resistance. Journal of Clinical Medicine, 11(21), 6491. https://doi.org/10.3390/jcm11216491

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