Aberrant Expression of <i>TLR2</i>,<i> TLR7</i>, <i>TLR9</i>, Splicing Variants of <i>TLR4</i> and <i>MYD88</i> in Chronic Lymphocytic Leukemia Patients

• Main Authors: Katarzyna Skorka, Paulina Wlasiuk, Agnieszka Karczmarczyk, Krzysztof Giannopoulos
• Format: Article
• Language: English
• Published: MDPI AG 2021-02-01
• Series: Journal of Clinical Medicine
• Subjects: CLL (chronic lymphocytic leukemia); TLRs (toll-like receptors); Myd88 (myeloid differentiation primary response protein 88)
• Online Access: https://www.mdpi.com/2077-0383/10/4/867

Functional toll-like receptors (TLRs) could modulate anti-tumor effects by activating inflammatory cytokines and the cytotoxic T-cells response. However, excessive TLR expression could promote tumor progression, since TLR-induced inflammation might stimulate cancer cells expansion into the microenvironment. Myd88 is involved in activation NF-κB through TLRs downstream signaling, hence in the current study we provided, for the first time, a complex characterization of expression of <i>TLR2</i>, <i>TLR4, TLR7</i>, <i>TLR9</i>, and <i>MYD88 </i>as well as their splicing forms in two distinct compartments of the microenvironment of chronic lymphocytic leukemia (CLL): peripheral blood and bone marrow. We found correlations between <i>MYD88</i> and <i>TLRs</i> expressions in both compartments, indicating their relevant cooperation in CLL. The <i>MYD88</i> expression was higher in CLL patients compared to healthy volunteers (HVs) (0.1780 vs. 0.128, <i>p </i>< 0.0001). The TLRs expression was aberrant in CLL compared to HVs. Analysis of survival curves revealed a shorter time to first treatment in the group of patients with low level of <i>TLR4(3)</i> expression compared to high level of <i>TLR4(3)</i> expression in bone marrow (13 months vs. 48 months, <i>p </i>= 0.0207). We suggest that <i>TLRs</i> expression is differentially regulated in CLL but is similarly shared between two distinct compartments of the microenvironment.