scholarly journals Old and Young Actors Playing Novel Roles in the Drama of Multiple Myeloma Bone Marrow Microenvironment Dependent Drug Resistance

2018 ◽  
Vol 19 (5) ◽  
pp. 1512 ◽  
Author(s):  
Sabrina Manni ◽  
Marilena Carrino ◽  
Gianpietro Semenzato ◽  
Francesco Piazza
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Drug Resistance ◽  
Bone Marrow Microenvironment

scholarly journals APRIL and BCMA promote human multiple myeloma growth and immunosuppression in the bone marrow microenvironment

Blood ◽  
2016 ◽  
Vol 127 (25) ◽  
pp. 3225-3236 ◽  
Author(s):  
Yu-Tzu Tai ◽  
Chirag Acharya ◽  
Gang An ◽  
Michele Moschetta ◽  
Mike Y. Zhong ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Drug Resistance ◽  
Bone Marrow Microenvironment ◽  
Key Points ◽  
Human Multiple Myeloma

Key Points APRIL/BCMA activation promotes MM proliferation, survival, and immunosuppression in vitro and in vivo. Targeting the APRIL/BCMA pathway represents a promising mechanism-based immunotherapy to target MM and overcome drug resistance.

scholarly journals NRF2 Is One of the Players Involved in Bone Marrow Mediated Drug Resistance in Multiple Myeloma

2018 ◽  
Vol 19 (11) ◽  
pp. 3503 ◽  
Author(s):  
Chia-Hung Yen ◽  
Hui-Hua Hsiao
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Drug Resistance ◽  
Hematologic Malignancy ◽  
Suppressor Cells ◽  
Resistance Mechanisms ◽  
Bone Marrow Microenvironment ◽  
Myeloma Cells ◽  
Functional Roles ◽  
Oxidative Stresses

Multiple myeloma with clonal plasma expansion in bone marrow is the second most common hematologic malignancy in the world. Though the improvement of outcomes from the achievement of novel agents in recent decades, the disease progresses and leads to death eventually due to the elusive nature of myeloma cells and resistance mechanisms to therapeutic agents. In addition to the molecular and genetic basis of resistance pathomechanisms, the bone marrow microenvironment also contributes to disease progression and confers drug resistance in myeloma cells. In this review, we focus on the current state of the literature in terms of critical bone marrow microenvironment components, including soluble factors, cell adhesion mechanisms, and other cellular components. Transcriptional factor nuclear factor erythroid-derived-2-like 2 (NRF2), a central regulator for anti-oxidative stresses and detoxification, is implicated in chemoresistance in several cancers. The functional roles of NRF2 in myeloid-derived suppressor cells and multiple myeloma cells, and the potential of targeting NRF2 for overcoming microenvironment-mediated drug resistance in multiple myeloma are also discussed.

scholarly journals Mechanisms of Drug Resistance in Relapse and Refractory Multiple Myeloma

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Wen-Chi Yang ◽  
Sheng-Fung Lin
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Drug Resistance ◽  
Hematological Malignancy ◽  
Clonal Evolution ◽  
Resistance Mechanisms ◽  
Bone Marrow Microenvironment ◽  
Molecular Targeting ◽  
Resistance To Therapy ◽  
Programmed Death

Multiple myeloma (MM) is a hematological malignancy that remains incurable because most patients eventually relapse or become refractory to current treatments. Although the treatments have improved, the major problem in MM is resistance to therapy. Clonal evolution of MM cells and bone marrow microenvironment changes contribute to drug resistance. Some mechanisms affect both MM cells and microenvironment, including the up- and downregulation of microRNAs and programmed death factor 1 (PD-1)/PD-L1 interaction. Here, we review the pathogenesis of MM cells and bone marrow microenvironment and highlight possible drug resistance mechanisms. We also review a potential molecular targeting treatment and immunotherapy for patients with refractory or relapse MM.

scholarly journals Mesenchymal stem cells from bone marrow regulate invasion and drug resistance of multiple myeloma cells by secreting chemokine CXCL13

2019 ◽  
Author(s):  
Guihua Zhang ◽  
Faan Miao ◽  
Jinge Xu ◽  
Rui Wang
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Drug Resistance ◽  
Mesenchymal Stem Cells ◽  
Western Blot ◽  
Plasma Cells ◽  
Bone Marrow Microenvironment ◽  
Protein Expressions ◽  
Mdr 1

Multiple myeloma (MM) is a hematologic cancer arising from plasma cells. Mesenchymal stem cells (MSCs) are a heterogeneous cell population in the bone marrow microenvironment. In this study, we evaluated the regulatory effects of MSCs on the invasion and drug resistance of MM cells U266 and LP-1. Bone marrow samples from MM patients and normal subjects were collected. MSCs were extracted from bone marrow and cultured, and their phenotypes were identified by flow cytometry. The level of CXCL13 in the supernatant of cultured MSCs was detected by ELISA. The protein expression of CXCR5 (a specific receptor of CXCL13) in U266 and LP-1 cells was detected by Western blot. The effects of MSCs on the invasion of U266 and LP-1 cells and the resistance to bortezomib were assessed by Transwell and CCK-8 assay, respectively. The mRNA and protein expressions of BTK, NF-κB, BCL-2, and MDR-1 were detected by RT-PCR and Western blot, respectively. CXCL13 was secreted by MSCs in the bone marrow microenvironment, and the level in MSCs from MM patients was significantly higher than that of healthy subjects. CXCR5 was expressed in both U266 and LP-1 cells. The resistance of MM cells to bortezomib was enhanced by MSCs through CXCL13 secretion. The invasion and proliferation of U266 and LP-1 cells were promoted, and the mRNA and protein expressions of BTK, NF-κB, BCL-2, and MDR-1 were upregulated by MSCs. The basic biological functions of MM cells U266 and LP-1 were affected by MSCs via the CXCL13-mediated signaling pathway. This study provides valuable experimental evidence for clinical MM therapy.

Exosome-derived miR-let-7c promotes angiogenesis in multiple myeloma by polarizing M2 macrophages in the bone marrow microenvironment

2021 ◽  
Vol 105 ◽  
pp. 106566
Author(s):  
Xiangyu Tian ◽  
Miaomiao Sun ◽  
Han Wu ◽  
Chao Chen ◽  
Hui Li ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Bone Marrow Microenvironment ◽  
M2 Macrophages
Sign in / Sign up

Export Citation Format

Share Document