Bhowmick Kuntal, von Suskil Max, Al-Odat Omar S, Elbezanti Weam Othman, Jonnalagadda Subash C, Budak-Alpdogan Tulin, Pandey Manoj K
Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, USA.
Department of Hematology, MD Anderson Cancer Center at Cooper, Cooper University Health Care, Camden, NJ, USA.
Heliyon. 2024 Jun 14;10(12):e33091. doi: 10.1016/j.heliyon.2024.e33091. eCollection 2024 Jun 30.
Multiple Myeloma (MM) is a malignant expansion of plasma cells in the bone marrow (BM), resulting in a disease characterized by symptoms of end organ damage from light chain secretion, crowding of the BM, and bone lesions. Although the past two decades have been characterized by numerous novel therapies emerging, the disease remains incurable due to intrinsic or acquired drug resistance. A major player in MM's drug resistance arises from its intimate relationship with the BM microenvironment (BMME). Through stress-inducing conditions, soluble messengers, and physical adhesion to BM elements, the BMME activates numerous pathways in the myeloma cell. This not only propagates myeloma progression through survival and growth signals, but also specific mechanisms to circumvent therapeutic actions. In this review, we provide an overview of the BMME, the role of individual components in MM survival, and various therapy-specific resistance mechanisms reported in the literature.
多发性骨髓瘤（MM）是骨髓（BM）中浆细胞的恶性增殖，导致一种以轻链分泌引起的终末器官损伤症状、骨髓拥挤和骨病变为特征的疾病。尽管在过去二十年中出现了众多新型疗法，但由于内在或获得性耐药，该疾病仍然无法治愈。MM耐药的一个主要因素源于其与骨髓微环境（BMME）的密切关系。通过应激诱导条件、可溶性信号分子以及与骨髓成分的物理粘附，BMME激活骨髓瘤细胞中的众多信号通路。这不仅通过生存和生长信号促进骨髓瘤进展，还通过特定机制规避治疗作用。在本综述中，我们概述了BMME、其各个组成部分在MM生存中的作用以及文献中报道的各种特定疗法的耐药机制。
