Association between TLR2 and TLR4 Expression and Response to Induction Therapy in Acute Myeloid Leukemia Patients

Abstract

Background: Toll-like receptors (TLRs) are a family of transmembrane pattern-recognition receptors that play a crucial role in the realization of innate and adaptive immune response. TLRs may play a role in tumor development and growth because of expression or up-regulation of functional TLRs in some tumors and tumor cell lines. The participation of TLRs in the pathogenesis of acute myeloid leukemia (AML) remains unspecified. This study aimed to investigate the effect of TLR2 and TLR4 expression in peripheral blood mononuclear cells of AML patients in response to induction chemotherapy. Materials and Methods: Eighty- five patients with newly diagnosed AML were evaluated. Using quantitative reverse transcriptase PCR, the mRNA expression of genes TLR2 and TLR4 was measured before starting and after induction chemotherapy. The differences in the mean expression levels of TLR2 and TLR4 before and after chemotherapy were compared using a paired t-test. The mean expression levels of TLR2 and TLR4 regarding laboratory data were analyzed by one-way ANOVA and Chi-square test. Results: We found that the mRNA expression of TLR2 after induction chemotherapy was significantly lower as compared to before treatment (p=0.001). Also, we found a lower TLR4 gene expression level after chemotherapy as compared to before chemotherapy, albeit it was not statistically significant (p=0.21). Moreover, we observed significantly higher expression of TLR2 and TLR4 in AML-M3 cases compared to non-M3 AML patients. Conclusion: The decreased expression of TLR4 in leukemic samples after induction chemotherapy might indicate a novel potential prognostic role for this receptor, particularly in AML-M3 cases.

Functional Toll-Like Receptors (TLRs) Are Expressed by a Majority of Primary Human Acute Myeloid Leukemia Cells and Inducibility of the TLR Signaling Pathway Is Associated with a More Favorable Phenotype

“…As summarized in the Introduction, previous studies of TLRs in AML have mainly focused on cell proliferation and survival, and several of these studies were mainly based on the use of cell lines [12,13,14,15,16,17]. In the present study, we therefore focused on detection of functional receptors and mRNA expression of TLRs and proteins downstream in the signaling pathway.…”

“…Of note, we did not detect TLR2 to be differentially expressed within our cohort. High mRNA expression of this particular receptor was in a previous study linked both with shorter overall survival and less response towards treatment [13], whereas another study reported reduced TLR2 mRNA levels at remission, but could not link TLR2 expression at diagnosis with patient survival [12].…”

“…Previous studies suggest that TLRs are expressed by various hematological malignant cells, including AML cells, and TLR agonists may therefore have direct effects on the leukemic cells [11]. First, primary AML cells seem to have increased levels of TLR2 and TLR4 [12], which then are associated both with chemoresistance and monocytic differentiation [13]. Second, several TLRs are also expressed in AML cell lines and specific receptor agonists seem to employ growth-inhibitory and pro-apoptotic effects in some of the cell lines [13,14].…”

Mechanisms underlying CD19-positive ALL relapse after anti-CD19 CAR T cell therapy and associated strategies

“…Moreover, Toll-like receptors (TLRs) play an important role in the immune response. It has been showed that after induction chemotherapy, the mRNA expression of TLR2 was significantly lower as compared to before treatment [56]. There are many other costimulatory domains, such as Dap10 costimulatory domains, 2B4 costimulatory domains, GITR domains, CD150 signaling lymphocytic activation molecule (SLAM), a 150-kDa protein termed as M150.…”

Immune prognostic risk score model in acute myeloid leukemia with normal karyotype

“…The significance of IRGs in AML progression and immunotherapeutics have been reported previously (22,23). However, to the best of our knowledge, no comprehensive, genome-wide profiling analysis of the prognostic significance of all IRGs in NK-AML has so far been performed.…”