In chronic lymphocytic leukemia, activation of the thrombopoietin receptor promotes T‐cell inhibitory properties, contributing to immunosuppression.

In chronic lymphocytic leukemia (CLL), the immune system is skewed towards a suppressive milieu. Levels of thrombopoietin (TPO), promoting cellular immune regulatory activity in immune thrombocytopenic purpura, were shown to be elevated in CLL patients. This study explored TPO as a potential immunomodulator, supporting CLL progression. We evaluated CLL cell‐induced expression of TPO receptor (TPO‐R) on T‐cells and effects of its activation on T‐cell responses. CLL cell involvement in TPO generation was also assessed. Baseline TPO‐R expression on CD4 + T‐cells was found to be higher in CLL patients than in healthy controls (HC). Exposure of HC‐T‐cells to B‐cells, especially to CLL‐B‐cells stimulated with B‐cell activating molecules, resulted in enhanced TPO‐R expression on T‐cells. CLL‐T‐cell stimulation with TPO reduced their proliferation and expanded the regulatory T‐cell (Treg) population. At baseline, phosphorylation of STAT5, known to impact the Treg phenotype, was elevated in CLL‐T‐cells relative to those of HC. Exposure to TPO further enhanced STAT5 phosphorylation in CLL‐T‐cells, possibly driving the observed Treg expansion. The CLL immune milieu is involved in promotion of inhibitory features in T‐cells through increased TPO‐R levels and TPO‐induced intracellular signaling. TPO and its signaling pathway could potentially support immunosuppression in CLL, and may emerge as novel therapeutic targets. [ABSTRACT FROM AUTHOR]