Higher proportion of non-classical and intermediate monocytes in newly diagnosed multiple myeloma patients in Egypt: A possible prognostic marker

Abstract

Background: Interaction between multiple myeloma (MM) cells and proximal monocytes is expected during plasma cell proliferation. However, the role of monocyte subsets in the disease progression is unknown.Objective: This study evaluated circulating monocyte populations in MM patients and their correlation with disease severity.Methods: Peripheral monocytes from 20 patients with MM attending Assiut University Hospital in Assiut, Egypt, between October 2018 and August 2019 were processed using a flow cytometry procedure and stratified using the intensity of expression of CD14 and CD16 into classical (CD16−CD14++), intermediate (CD16+CD14++), and non-classical (CD16++CD14+) subsets. The data were compared with data from 20 healthy control participants with comparable age and sex.Results: In patients with MM, the percentage of classical monocytes was significantly lower (mean ± standard error: 77.24 ± 0.66 vs 83.75 ± 0.5), while those of non-classical (12.44 ± 0.5 vs 8.9 ± 0.34) and intermediate (10.3 ± 0.24 vs 7.4 ± 0.29) monocytes were significantly higher when compared with those of controls (all p 0.0001). Proportions of non-classical and intermediate monocytes correlated positively with serum levels of plasma cells, M-protein, calcium, creatinine and lactate dehydrogenase, and correlated negatively with the serum albumin level. Proportions of classical monocytes correlated positively with albumin level and negatively correlated with serum levels of M-protein, plasma cells, calcium, creatinine, and lactate dehydrogenase.Conclusion: Circulating monocyte subpopulations are skewed towards non-classical and intermediate monocytes in MM patients, and the intensity of this skewness increases with disease severity.

Immunophenotypic correlates of sustained MRD negativity in patients with multiple myeloma

“…Our results support prior observations showing that the percentage of classical monocytes is reduced in patients with MM compared to healthy controls 32 . This appears to be independent of the history of HDM-ASCT, as classical monocytes are reduced even in patients who have not undergone a transplant.…”

Single‐cell atlas of the immune microenvironment reveals macrophage reprogramming and the potential dual macrophage‐targeted strategy in multiple myeloma

“…Among CD14 + subsets, hm1 was annotated as CD14 + monocyte‐FCN1 featured by high expression of FCN1 and low expression of CD163, while hm4 and hm5 characterized by high CD163 expression were defined as MPs (Figure 3C). Non‐classical CD16 + CD14 − monocytes were reported to be enriched in MM and associated with tumour burden 12,36 . In our data, the proportions of CD16 + subsets (hm3, hm6) exhibited heterogeneous distribution among individuals (Figure 3D, right) with a tendency to be enriched in early‐stage (MGUS) and late‐stage disease (RRMM, Figure 3D, left).…”

“…Non-classical CD16 + CD14 − monocytes were reported to be enriched in MM and associated with tumour burden. 12,36 In our data, the proportions of CD16 + subsets (hm3, hm6) exhibited heterogeneous distribution among individuals (Figure 3D, right) with a tendency to be enriched in early-stage (MGUS) and late-stage disease (RRMM, Figure 3D, left).…”

Definers and drivers of functional high-risk multiple myeloma: insights from genomic, transcriptomic, and immune profiling

“…In contrast, high levels of circulating monocytes have been a poor prognostic feature in several studies ( 62 , 63 ). The types of monocytes within the blood and marrow may matter as much as their quantities, given that non-classical monocytes (CD16+CD14 dim ) may drive myeloma cell growth and increased tumor burden ( 64 , 65 ). In contrast, classical monocytes (CD14+CD16-) may have the opposite effect ( 66 , 67 ).…”