The Role of the Bone Marrow Microenvironment in Multiple Myeloma Evolution and Therapy

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About this Research Topic

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Background

Multiple Myeloma (MM) is a hematologic malignancy of aberrant plasma cells (PC) that reside within the bone marrow (BM). Despite the advent of novel therapies, MM remains largely incurable and the disease course is characterized by a relapsing pattern ultimately leading to refractory disease and patient death. Tumor-intrinsic factors alone cannot explain the difference in progression rates, emphasizing the role of extrinsic factors. This assumption is supported by the fact that the surrounding BM microenvironment (BM-ME) has been shown to impact differentiation, proliferation, and survival of aberrant PCs. More importantly, some of these changes have been linked to relapse and treatment resistance of MM ultimately influencing patient survival.

The composition of the BM-ME affects the development of MM from its precursor stages monoclonal gammopathy of undetermined significance (MGUS) and Smoldering MM (SMM), as well as disease progression and treatment response in clinical MM. Because MM tumor growth relies heavily on its surrounding BM microenvironment, targeting cellular and extracellular components of the BM niche has become a vital treatment strategy. Despite the vast amount of studies on the BM-ME in MM, our understanding of molecular alterations and the comprehensive networking within the microenvironment still remains limited. This knowledge would be important to 1. identify therapeutic mechanisms of early intervention in patients who progress from precursor stages to clinical MM and 2. to optimize current therapeutic approaches in clinical MM to prevent disease relapse, particularly in the light of emerging immunotherapies.

In this Research Topic we would like to summarize recent knowledge and new perspectives about alterations of the MM surrounding BM-ME that contribute to tumor growth and disease relapse. We further would like to outline how BM-ME can be targeted therapeutically to delay progression from MGUS/SMM to MM and to improve MM outcomes. The goal of this Research Topic is to address a variety of cell subsets within the BM-ME, including, but not limited to, immune cells, osteoblasts/osteoclasts, and stromal cells. We welcome Original Articles, Reviews, Systematic Reviews, Clinical Trials, and Case Reports focused on the following themes:

1) Identifying the role of the BM-ME in the transitioning from the precursor stages MGUS and SMM to clinical MM.

2) Determining the importance of the BM-ME in MM progression and treatment resistance.

Please note: manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) will not be accepted in any of the sections of Frontiers in Oncology.

Keywords: Multiple Myeloma, Microenvironment, Bone Marrow niche, Immune cells, Osteoclasts/Osteoblasts, Mesenchymal cells

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