title: 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.
authors.affiliation: Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, ul. Pasteura 4, 50-367, Wrocław, Poland, rybka.justyna@o2.pl.
authors.forename: Justyna
authors.initials: J
authors.lastname: Rybka
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Butrym
authors.forename: Tomasz
authors.initials: T
authors.lastname: Wróbel
authors.forename: Bożena
authors.initials: B
authors.lastname: Jaźwiec
authors.forename: Ewa
authors.initials: E
authors.lastname: Stefanko
authors.forename: Olga
authors.initials: O
authors.lastname: Dobrzyńska
authors.forename: Rafał
authors.initials: R
authors.lastname: Poręba
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Kuliczkowski
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016470:Bacteremia / Q000235:genetics; D064147:Febrile Neutropenia; D005260:Female; D016469:Fungemia / Q000235:genetics; D006801:Humans; D060828:Induction Chemotherapy; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D018805:Sepsis / Q000209:etiology*; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics; D051217:Toll-Like Receptor 9 / Q000235:genetics; D051193:Toll-Like Receptors / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C495342:TLR2 protein, human; C495345:TLR4 protein, human; C495371:TLR9 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors