The blood test parameter monocyte-to-lymphocyte ratio (MLR) may serve as a useful marker of activity in chronic lymphocytic leukemia (CLL), a new report has found.1 The findings, which were reported in the International Journal of Inflammation, also suggest that MLR can be used to better understand changes in the monocyte subpopulations in the blood microenvironment.
Inflammation in the tumor microenvironment is believed to play a role in the initiation and progression of CLL, the authors explained. For instance, previous research found patients with CLL who had low monocyte counts had a higher risk of mortality, largely due to infectious complications.
Yet, the precise nature of the connection between inflammation and progression is not yet clear. At present, the authors said, the primary method of assessing inflammation in the blood is through inflammatory markers in the peripheral blood.
Overall, participants with CLL had significantly lower MLR values compared with the healthy donors. | Image credit: angellodeco – stock.adobe.com
“However, in the age of modern technology, a more detailed analysis of inflammatory cells circulating in the blood of CLL patients would be useful,” they wrote.
In the new study, the researchers sought to undertake a more thorough analysis of MLR to see whether it aligned with the patient’s risk of progression. They also aimed to determine whether MLR values might correlate with the functional immune status of circulating monocyte subsets.
The investigators gathered peripheral blood samples from 54 patients who were newly diagnosed with CLL and had not yet received treatment. They then compared those with samples from 20 healthy volunteers.
The samples were assessed by multiparametric flow cytometry and evaluated for both surface markers and intracellular expression of cytokines. They also used fluorescence-activated cell sorting to determine the relative expression of certain microRNA.
Overall, participants with CLL had significantly lower MLR values (median [IQR], 0.04 [0.095-0.02]) compared with the healthy donors (median [IQR], 0.265 [0.318-0.23]; P < .0001). Patients with stage III or IV CLL had significantly higher MLR values (median [IQR], 0.1 [0.23-0.07]), compared with those with stage 0 disease (median [IQR], 0.03 [0.06-0.01]; P < .01). Similarly, patients with negative clinical and laboratory prognostic factors—such as an increased percentage of CD5+/CD19+ cells with ZAP-70 and CD38 expression—also had higher MLR values.
The investigators next split the patients with CLL into MLR-high and MLR-low groups. The groups had 13 and 41 patients, respectively. The results showed that the MLR-high group had a significantly higher percentage of intermediate monocytes, but a significantly lower percentage of classical and nonclassical monocytes. They also found other differences.
“In our study, in MLR-high CLL patients with poor prognostic factors, that is, increased expression of CD38 and ZAP-70 in leukemic cells, we observed a significantly lower percentage of nonclassical monocytes with intracellular TNF (tumor necrosis factor) expression and a significantly higher percentage of intermediate monocytes with intracellular IL-10 expression, allowing us to see a correlation between the functional maturation of the circulating monocytes and the degree of disease progression,” they explained.
In addition, they found that the expression of miR-106a, miR-150-5p, and miR-21-3p was significantly different between the healthy patients and those with CLL, “which may suggest that the inflammatory conditions prevailing in the course of CLL also affect the mechanisms dependent on these miRNAs determining monocyte subpopulation heterogeneity,” they wrote.
The authors noted their study’s limitations included the fact that it featured a relatively small number of participants and also focused exclusively on newly diagnosed patients.
They said, however, that their findings suggest that MLR can be useful in obtaining information about the phenotypic and functional immune status of monocyte subpopulations in the blood of patients with CLL.
References
1. Grzegorzewska W, Zarobkiewicz M, Jastrzębska-Pawłowska K, et al. MLR corresponds to the functional status of monocytes in chronic lymphocytic leukemia. Int J Inflamm. 2025;2025(1):4443773. doi:10.1155/ijin/4443773
2. Szerafin L, Jakó J, Riskó F. Az abszolút monocytaszám prognosztikus értéke krónikus lymphoid leukaemiában [Prognostic value of absolute monocyte count in chronic lymphocytic leukaemia]. Orv Hetil. 2015;156(15):592-597. doi:10.1556/OH.2015.30126