The Immune Microenvironment in Multiple Myeloma Progression at a Single-cell Level

ultiple myeloma (MM) is a hematological malig- nancy of aberrant clonal plasma cells that reside within the bone marrow (BM). 1 The disease course differs from other BM malignancies essentially in 2 features. First, there are 2 precursor stages, monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM (SMM), that can transition into MM over time. 2 Second, once clinical MM develops, the disease remains largely incur- able, and despite significant therapeutic improvements, relapse and refractoriness usually cannot be prevented. The interactions between MM cells and the BM microenvironment (BM-ME) are an area of particularly intense research, as tumor evasion and suppression of the host immune system constellate main factors of MM progression. 3 Single-cell sequencing technologies that have emerged over the last years have the potential to significantly advance the field because they enable the evaluation of alterations in cell numbers and states as well as interac- tions between MM cells and the BM-ME. Recent studies have applied single-cell techniques at different precursor and MM stages to determine the comprehensive changes in the BM-ME and to identify mechanisms that foster oncogenesis. 4–11 This article briefly summarizes these studies and proposes how the dissection of the BM-ME on a single-cell level can improve our understanding of MM pathogenesis, thereby advancing prog- nostication and the therapeutic landscape. We would like to emphasize that single-cell analyses are a rapidly expanding field and the number of published studies investigating the BM-ME in MM and its precursors is likely to grow exponentially in the next few years given the increased interest in and access to single-cell technologies. Thus, this perspective does not cover all available articles.