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. 2024 Oct-Dec;46(4):374-380.
doi: 10.1016/j.htct.2023.05.005. Epub 2023 Jul 6.

IL-8 in bone marrow and peripheral blood of patients with B-cell acute lymphoblastic leukemia is associated with high regulatory T cell counts, degree of tumor infiltration and expression of CXCR1 in blasts

Diana Anaya  1 , Sandra Paola Santander González  1 , Natalia Murillo  1 , Ricardo Ballesteros-Ramírez  1 , Iliana De Los Reyes  2 , María V Herrera  2 , Julio Solano  2 , Susana Fiorentino  1 , Sandra Quijano  3
Affiliations

IL-8 in bone marrow and peripheral blood of patients with B-cell acute lymphoblastic leukemia is associated with high regulatory T cell counts, degree of tumor infiltration and expression of CXCR1 in blasts

Diana Anaya et al. Hematol Transfus Cell Ther. 2024 Oct-Dec.

Abstract

Introduction: Regulatory T cells (Treg cells) in a tumor environment and the expression of forkhead box P3 (FOXP3) in tumor cells have been associated with a poor prognosis. There are few studies evaluating Treg cells and FOXP3 in B-cell acute lymphoblastic leukemia (B-cell ALL). This study aimed to evaluate the frequencies of Treg cells in bone marrow (BM) and peripheral blood (PB) of patients with B-cell ALL and to determine their associations with the circulating cytokine profile and the expression of CXCR1 (IL-8 receptor) in Treg cells, as well as to compare FOXP3 expression in blasts of patients with B-cell ALL and normal lymphoid precursors.

Methods: Samples of BM and PB from patients with B-cell ALL and healthy controls were studied. Treg cells, cytokines, FOXP3 and CXCR1 were evaluated using flow cytometry and analyzed.

Results: A total of 20 patients with B-cell ALL and 10 healthy controls were included. In B-cell ALL patients, Treg cell frequencies increased significantly, with higher percentages in the PB. Absolute Treg cell counts were associated with absolute blast counts in the BM and PB and with an IL-8 concentration. The IL-8 and IL-6 levels were associated with the CXCR1 expression in PB Treg cells. In addition, a greater expression of FOXP3 was observed in leukemic blasts than in normal lymphoid precursors.

Conclusions: These results suggest that the presence of Treg cells and cytokines in the tumor environment may correspond to mechanisms to evade the immune response. For that reason, it would be important to monitor these parameters in B-cell ALL to establish their effect on the disease prognosis.

Keywords: B-cell acute lymphoblastic leukemia; Cytokines; Flow cytometry; IL-8; Regulatory T cells.

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Conflict of interest statement

Conflicts of interest None.

Figures

Figure 1
Figure 1
Comparative analysis of relative frequencies (panel A) and absolute numbers (panel B) of Treg cells (CD25high/FoxP3+) in BM and PB of patients with B-cell ALL and controls; and comparative analysis of Treg cells in BM and PB (panels C and D). Box and whisker charts extend to the 5th and 95th percentiles. Differences were determined by non-parametric tests. *p<0.05 compared to controls.
Figure 2
Figure 2
Plasma levels of IL-6 (A), IL-8 (B) and IL-10 (C) from BM and PB samples from patients with B-cell ALL and controls. Box and whisker charts extend to the 5th and 95th percentiles. The differences between them were determined by non-parametric tests. *p<0.05 compared to controls.
Figure 3
Figure 3
Expression of FoxP3 and CXCR1 in BM and PB cells. FoxP3 MFC in different cell populations of BM (A) and the ratio of FoxP3 MFC from a cell subset to FoxP3 MFC of Treg cells in BM of the same sample (BM/MFC) (B). *p<0.05 compared to CD34+ cells. ** p<0.05 compared to erythroblasts (red lineage). +p<0.05 compared to Treg cells. The percentage of CXCR1 MFC (C) cells in BM blasts of patients with B-cell ALL was compared with the values of neutrophils and lymphoid populations in PB of controls; *p<0.05. We compared the percentage of CXCR1+ (D) and CXCR1 MFC (E) cells in BM and PB blasts of patients with B-cell ALL. *p<0.05. Box and whisker charts extend to the 5th and 95th percentiles. ns: p value not significant
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