Evaluation of Interleukin-9 Expression as a Potential Therapeutic Target in Chronic Lymphocytic Leukemia in a Cohort of Egyptian Patients

Abstract

There was an overexpression of IL-9 in CLL patients that correlated with modified Rai staging, ZAP70, CD38 and all hallmarks of an active and aggressive disease. The correlation between IL-9 upregulation and patient characteristics provided direct clinical evidence for its contribution to the pathogenesis of CLL. In conclusion, significantly higher expression of IL-9 measured at both the mRNA and the protein levels in patients with CLL that correlates with more complex course of the disease and worse prognosis may allow one to speculate its importance in the pathogenesis of the disease and its possible impact on prognosis.

Clinico-Biological Implications of Modified Levels of Cytokines in Chronic Lymphocytic Leukemia: A Possible Therapeutic Role

“…The altered expression of IL-9 evaluated at both the mRNA and protein levels has been reported in biopsies and in the serum of B-CLL patients [127]. This increase correlated with Rai staging, ZAP70, and CD38 [128].…”

Interleukin (IL)-9 Supports the Tumor-Promoting Environment of Chronic Lymphocytic Leukemia

“…Intravenous injection of monoclonal anti-IL-9 antibodies was proven effective in ameliorating disease outcomes in the Eμ-TCL1/p66Shc −/− mouse model of aggressive CLL [ 15 ], paving the way to further pre-clinical studies. In the era of targeted therapies, the strong association between circulating IL-9 and markers of unfavorable CLL prognosis [ 14 , 15 , 90 ] suggests the potential use of anti-IL-9 antibodies as a therapeutic option for patients with high IL-9 levels. Interestingly glucocorticoids, potent immune-suppressive agents that reduce cytokine expression by inhibiting transcription factors such as Activation Protein (AP)-1 and NF-κB, have been observed to reduce IL-9 expression in asthma patients [ 40 , 105 ].…”

“…We and others recently reported the overexpression of IL-9 in leukemic cells from CLL patients [ 14 , 15 , 90 , 91 , 92 ] and Eμ-TCL1 mice [ 15 ], a well-established CLL mouse model [ 93 ]. Interestingly, this enhanced expression correlates with hallmarks of aggressive disease, such as unmutated Immunoglobulin Heavy Variable (IgHV) genes, ectopic expression of ζ-associated protein of 70 kDa (ZAP-70), and high levels of the surface glycoprotein CD38 [ 14 , 15 , 90 ]. Moreover, it correlates with lower overall survival of CLL patients [ 15 ].…”

“…These findings indicate that, in the specific context of CLL, IL-9 is overexpressed not only by Th9 cells, but also by leukemic cells themselves. Irrespective of the cells involved in the secretion of this cytokine, the increased amount of IL-9 in the CLL tumor microenvironment has been proven to promote tumor development [ 14 , 15 , 90 , 91 ]. To date, the effects of this cytokine on the immune components of the tumor microenvironment have not been investigated.…”

Assessment of Impact of Human Leukocyte Antigen-Type and Cytokine-Type Responses on Outcomes after Targeted Therapy Currently Used to Treat Chronic Lymphocytic Leukemia

“…Research has revealed that IL-9 plays a role in neoplastic proliferation, particularly in lymphomagenesis [ 13 ]. Studies examined biopsies and serum samples from patients with B-cell chronic lymphocytic leukemia (CLL) and found that the levels of IL-9 mRNA and protein expression were altered and correlated with Rai staging, ZAP70, and CD38 [ 28 ]. This was confirmed in further studies, where IL-9 expression was detected in the serum of 20 out of 47 CLL patients but was not detectable in control subjects [ 29 ].…”