MLR Corresponds to the Functional Status of Monocytes in Chronic Lymphocytic Leukemia

TL;DR

This study explores how the monocyte/lymphocyte ratio (MLR) reflects immune changes in chronic lymphocytic leukemia patients.

Contribution

The study links MLR to monocyte subset function and disease progression in CLL patients.

Findings

CLL patients had significantly lower MLR values compared to healthy volunteers.

MLR-high CLL patients showed increased intermediate monocytes with anti-inflammatory traits.

Intermediate monocytes in MLR-high patients had altered cytokine and miRNA expression.

Abstract

Background: The role of the inflammatory microenvironment in initiating and progressing chronic lymphocytic leukemia (CLL) is still not clarified. To date, it has been shown that the only way to reflect inflammation in the systemic circulation is to assess inflammatory markers in peripheral blood. However, in the age of modern technology, a more detailed analysis of inflammatory cells circulating in the blood of CLL patients would be useful.

Objectives: The study aimed to evaluate the relationship between one of the hematological inflammatory indexes—the monocyte/lymphocyte ratio (MLR) and the risk of CLL progression associated with disease activity. In addition, we wanted to analyze whether the MLR parameter in CLL could suggest the functional immune status of circulating main monocyte subsets.

Methods: The study included peripheral blood samples from 54 untreated, newly diagnosed CLL patients and 20 healthy volunteers (HVs). Immunological characterization of monocyte subpopulations included their detailed assessment by multiparametric flow cytometry, including evaluation of surface markers and intracellular expression of cytokines. In addition, the relative expression of selected microRNA (miR-21-3p, miR-150-5p, miR-106a-5p) was determined in FACS-sorted monocyte subsets.

Results: In our study, CLL patients had significantly lower values of MLR parameters compared to HVs (p < 0.0001). However, the value of MLR was higher in CLL patients with negative clinical and laboratory prognostic factors, i.e., increased percentage of CD5+/CD19+ cells with ZAP-70 and CD38 expression. We noticed that the percentage of intermediate monocytes is significantly higher, but classical and nonclassical ones are significantly lower in MLR-high compared to MLR-low CLL patients. Moreover, among the monocyte subsets circulating in the blood of MLR-high, ZAP-70+, and CD38+, CLL patients' intermediate monocytes were characterised by increased intracellular expression of IL-10 and decreased miR-150-5p relative expression compared to intermediate monocytes in the MLR-low, ZAP-70-, and CD38- groups, suggesting a potential link between hematological inflammatory index and the formation of intermediate monocytes that promote CLL burden.

Conclusions: The MLR index may serve not only as a marker of CLL activity, but also indirectly indicate changes in the phenotype and function of monocyte subpopulations present in the blood microenvironment. Moreover, the MLR-high parameter seems to correspond to an increase in the percentage of intermediate monocytes with anti-inflammatory properties, which may potentially promote disease progression and worsen its prognosis.

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