The expression of Toll-like receptors and development of severe sepsis in patients with acute myeloid leukemias after induction chemotherapy

Abstract

Toll-like receptors play an important role in the host defense against microorganisms. Sepsis remains a common cause of mortality in patients with acute myeloid leukemia (AML) treated with intensive induction chemotherapy. The expression of TLRs and their association with the development of sepsis in patients with acute myeloid leukemia remains unclear. The aim of this study was to investigate the associations between expression of TLR2, TLR4 and TLR9 and occurrence of sepsis in patients treated with intensive induction chemotherapy for AML. A total of 103 patients with newly diagnosed AML were evaluated. Bone marrow samples were taken before induction therapy. Using quantitative reverse transcriptase PCR, the mRNA expression of genes TLR2, TLR4 and TLR9 was measured. Neutropenic fever occurred in 98 patients. We identified 20 episodes of severe sepsis (20 %). In patients with neutropenic fever, the mRNA expression of TLR2 and TLR4 was significant higher in septic patients than in patients without sepsis symptoms (ΔCt TLR2 0.93 ± 0.82 vs 0.78 ± 0.85 and ΔCt TLR4 0.38 ± 0.29 vs 0.34 ± 0.25). Moreover, we observed that expression of TLR2 and TLR4 was significantly higher in patients with AML and bacterial infection in comparison with group with separate fungal infection (ΔCt TLR2 1.15 ± 1.06 vs 0.66 ± 0.51 and ΔCt TLR4 0.45 ± 0.38 vs 0.21 ± 0.19). Our results suggest that TLRs could be an independent factor for the development of sepsis in patients with acute myeloid leukemias after intensive induction chemotherapy. This observation should be validated by larger study.

Quantitative Expression of Toll-Like Receptors TLR-7 and TLR-9 on Peripheral Blood Mononuclear Cells in Leukemias

“…Our findings were similar to those of previous studies [8,20,21] which evaluated the quantitative expression of TLRs in patients with newly diagnosed or relapsed AML and concluded that the highest level of TLR expression was seen for TLR-7 while there was no significant difference in the expression of the other TLRs compared to the healthy volunteers. Similarly, other studies [6,22,23] demonstrated that the level of TLR-7/β-actin mRNA expression was significantly elevated in AML patients compared to normal cases (P < 0.05). Meanwhile there was no statistically significant difference between the level of TLR-9/β-actin mRNA expression in AML patients and in normal cases (P > 0.05).…”

Management of sepsis in neutropenic cancer patients: 2018 guidelines from the Infectious Diseases Working Party (AGIHO) and Intensive Care Working Party (iCHOP) of the German Society of Hematology and Medical Oncology (DGHO)

“…Evidently, Toll-like receptor (TLR) expression and polymorphism also seem to play a role in the development of sepsis. In patients with neutropenic fever, levels of mRNA expression of TLR2 and TLR4 were significantly higher in sepsis patients compared to patients without sepsis [7]. Further, polymorphisms of TLR2 and TLR4 influence the risk of infectious complications in patients with acute myeloid leukemia undergoing chemotherapy [8].…”

Variations in genes involved in regulation of the nuclear factor – κB pathway and the risk of acute myeloid leukaemia

“…Of note, expression of these both TLRs was reported by Rybka et al . (, ) as factors associated with the risk of sepsis and the outcome of induction therapy. Nevertheless, further genetic studies are indispensable to confirm the role of expression and polymorphisms of these two TLRs in development of infectious complications in patients with AML.…”

“…IL17F ) may be associated with AML susceptibility (Wróbel et al ., ). It was also found that TLR2 and TLR4 could act as risk factors for the development of sepsis and response to therapy in patients with AML (Rybka et al ., , ). The present study aimed to assess the effect of the polymorphisms in genes in the inflammatory pathways involved in regulation of the NF‐κB pathway ( TLR2 , TLR4 , TLR9 , TRAF3 and NFkB1 ) and susceptibility to AML and progression of the disease.…”