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[Expression and Clinical Significance of Helper T Cells 9 and Its Sytokines Interleukin 9 in Chronic Lymphocytic
Tudahong Shabaaiti1, Nan-Nan Pang2, Alimu Xierenguli1
1Hematologic Disease Center, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region Institute of Hematology, Urumqi 830054, Xinjiang Uygur Autonomous Region, China.
Insights
T helper 9 (Th9) cells and their cytokine, interleukin-9 (IL-9), are significantly elevated in chronic lymphocytic leukemia (CLL) patients. This increased expression correlates with poorer prognosis, indicating Th9/IL-9 as potential biomarkers for CLL progression.
Area of Science:
- Immunology
- Hematology
- Oncology
Context:
- Chronic lymphocytic leukemia (CLL) is a common B-cell malignancy.
- The role of T helper 9 (Th9) cells and their associated cytokine, interleukin-9 (IL-9), in CLL pathogenesis remains incompletely understood.
- Investigating novel cellular and molecular players is crucial for improving CLL management.
Purpose:
- To determine the expression levels of Th9 cells and IL-9 in the peripheral blood of CLL patients.
- To analyze the clinical significance and prognostic value of Th9 and IL-9 in relation to CLL staging and specific molecular markers.
- To explore the correlation between Th9 cell proportion, IL-9 levels, and clinicopathological features of CLL.
Summary:
- Flow cytometry, Western blot, and ELISA revealed significantly higher proportions of Th9 cells, and elevated expression of PU.1, IRF4, and IL-9 in CLL patients compared to healthy controls.
- Th9 and IL-9 levels were notably increased in advanced Binet stages (B and C) and associated with adverse prognostic indicators such as β2 microglobulin abnormality, IGHV unmutation, P53 abnormality, and hepatosplenic enlargement.
- Spearman correlation analysis demonstrated a positive correlation between Th9/IL-9 expression and disease staging (Binet, Rai, CLL-IPI), while Th9 proportion showed a negative correlation with lymphocyte count and proportion.
Impact:
- The findings suggest that elevated Th9 cells and IL-9 are characteristic of CLL and are linked to disease progression and poor prognosis.
- Th9 and IL-9 may serve as valuable biomarkers for assessing CLL severity and predicting patient outcomes.
- This research contributes to a deeper understanding of the immune microenvironment in CLL and highlights potential therapeutic targets.
Objective:
To investigate the expression and clinical significance of T helper cell 9 (Th9) and its cytokine interleukin 9(IL-9) in peripheral blood of patients with chronic lymphocytic leukemia(CLL).
Methods:
A total of 43 newly diagnosed patients with chronic lymphocytic leukemia in the First Affiliated Hospital of Xinjiang Medical University from June 2021 to June 2022 were selected as the case group. The patients were divided into Binet A group (13 cases), Binet B group (20 cases) and Binet C group (10 cases) by Binet staging system, and 20 healthy volunteers who underwent physical examinationin in our hospital in the same period served as control group. The proportion of Th9 cells in peripheral blood was detected by flow cytometry, the expression level of Th9 specific transcription factors PU.1 and IRF4 was detected by Western blot, and the expression level of serum cytokine IL-9 was detected by ELISA. The proportion of Th9, the expression of PU.1, IRF4 and IL-9 in each group were compared, and the correlation between the proportion of Th9, IL-9 and clinicopathological indexes of CLL patients was analyzed.
Results:
The proportion of Th9, the expression of PU.1, IRF4 and IL-9 in CLL group were significantly higher than those in control group (P<0.05), the proportion of Th9 and the expression of IL-9 in Binet B and C group were higher than those in Binet A group (P<0.05), but there was no significant difference in the proportion of Th9 cells between Binet B group and C group (P>0.05). The expression of IL-9 in Binet C group was significantly higher than that in Binet B group (P<0.05) . The proportion of Th9 cells and IL-9 were highly expression in patients with β2 microglobulin abnormality, IGHV unmutation, P53 abnormality and hepatosplenic lymph node enlargement(P<0.05), but not related to age and sex (P>0.05). The results of Spearman correlation analysis showed that the proportion of Th9 in patients with CLL was negatively correlated with the lymphocytic account and lymphocyte proportion(r=-0.32，r=-0.34). The proportion of Th9 and IL-9 were positively correlated with Binet stage, Rai stage and CLL-IPI Scoring (r=0.79，r=0.54，r=0.58； r=0.72，r=0.63，r=0.45), but not with WBC, CD4+ T cells and CD8+T cells (P>0.05). The proportion of Th9 was positively correlated with IL-9 (r=0.53).
Conclusion:
Th9 cells and IL-9 are abnormally highly expressed in CLL, which is related to the poor prognosis of CLL.
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