By Nathan Tidwell

Characterizing the role of the immune microenvironment in multiple myeloma progression at a single-cell level

Multiple myeloma (MM) is preceded by precursor stages including MGUS and smoldering myeloma. It is thought that the acquisition of mutations in the myeloma cells is responsible for disease progression through these stages. In this study, Dr. Schinke and colleagues study the bone marrow micro-environment, which are the non-myeloma cells of the bone marrow. The main premise of the study is that early alterations within the bone marrow microenvironment such as changes in immune cells contribute to the progression of multiple myeloma from its precursor stages. Identification of these changes in the immune system may be the key to identifying novel treatment approaches. Using a novel technique, Schinke, et al sequenced the genetic material in single cells from the bone marrow environment from monoclonal gammopathy of unknown significance, smoldering MM, and newly diagnosed MM patients. Changes in immune cell compostion were found such as a substantial decrease in memory and naïve help T-cells. There was also in and T-regulatory cells, which dampen the immune response. These alterations were further accompanied by an enrichment of nonclonal memory B cells and an increase in CD14 and CD16 monocytes in MM compared with its precursor stages. These early results provide crucial information on the immune changes associated with the progression to clinical MM and can help to develop immune-based strategies for patient stratification and early therapeutic intervention.

Concomitant deletion of the short arm (Del 1p13.3) and amplification or gain (1q21) of chromosome 1 by fluorescence in situ hybridization are associated with a poor clinical outcome in multiple myeloma

American Cancer Society Journals
June 2023
Primary author: Maurizio Zangari, M.D.

On the long arm of chromosome 1, genes are located that control cell growth and survival. For over two decades our group has drawn attention to the fact that multiple copies of these genes on chromosome 1 confer a poor prognosis. This has recently also been recognized by the International Myeloma Working Group. In this paper, Dr Zangari and colleagues focus on the loss of the short arm of chromosome 1 in 1133 patients treated on Total Therapy trials. Loss of the short arm of chromosome 1 occurred in 20% of patients and was associated with high risk features and worse survival. The presence of abnormalities of both the long and short arm of chromosome 1 was an especially poor feature. We have previously identified 70 genes by gene expression profiling that predict a worse outcome; many of these genes are located on chromosome 1. In the present study, fluorescent-in-situ hybrization (FISH) was used to detect chromosome 1 abnormalities. FISH is a widely-available technique compared to more complex gene expression profiling, and this knowledge will improve risk prediction for many myeloma patients. In addition, this study shows that it is not only the presence of abnormalities of the long arm of chromosome per se which is a poor prognostic predictor, but the context in which it occurs matters together with the loss of the short arm of chromosome 1.