No abstract

PurposeRecent studies have suggested that Th17 cells may play a role in the pathogenesis of acute myeloid leukemia (AML). This subset of CD4+ cells is characterized by interleukin (IL)-17A and IL-17F production, which share strong homology, and surface expression of the IL-23 receptor (IL-23R). The present study aimed to determine the association between the polymorphic features located within the IL-17A, IL-17F and IL-23R genes and disease susceptibility, progression and response to therapy. In addition, the relationship between the polymorphic variants and the plasma IL-17 levels in patients was analyzed.MethodsFor this purpose, 187 individuals of Polish origin including 62 AML patients and 125 healthy controls were typed for IL-17A (rs2275913; G-197A), IL-17F (rs763780; A7488G; His161Arg) and IL-23R (rs11209026, G1142A; Arg381Gln) alleles.ResultsThe rs763780 IL-17F polymorphism appeared to be associated with susceptibility to the disease. The presence of the minor (G) variant (RR = 4.76, p < 0.001) and its homozygosity (RR = 23.02, p < 0.005) was more frequent among patients than healthy individuals. No significant association was observed for either other polymorphisms studied or IL-17 levels.ConclusionsThus, the rs763780 IL-17F polymorphism was found to be associated with predisposition to AML in the Polish population.

We retrospectively analyzed long-term disease outcome of 350 elderly Hodgkin Lymphoma (eHL) patients treated with ABVD/ABVD-like regimen enrolled in the PLRG-R9 study between 2001 and 2013 in Poland. Complete remission was reported for 73% of early (ES) and 61% advanced stage (AS) patients. Nine (10%) ES and 56 (20%) AS patients have died. With the median follow-up of 36 (1-190) months, 3-year EFS and OS was 0.74 (95%CI: 0.63-0.85) and 0.90 (95%CI: 0.82-0.98) for ES; 0.51 (95%CI: 0.44-0.57), and 0.81 (95%CI: 0.75-0.86) for AS patients, respectively. For ES patients, Cox regression revealed ECOG <2 and age >70 as predictive for inferior OS and EFS. For AS patients, the most predictive for OS was the presence of cardiovascular disorders (CVD) (p = .00044), while for EFS four factors were significantly associated with a poor outcome: ECOG< 2, age >70 years, CVD and extranodal disease. In conclusion, CVD significantly impacts outcomes of ABVD-treated advanced eHL patients.

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.

MNS16A is a functional polymorphic tandem repeat within the human telomerase reverse transcriptase (hTERT) gene. To investigate whether any of the MNS16A repeats represents a genetic risk factor for NHL susceptibility, progression of or response to therapy in 75 patients with non-Hodgkin's lymphomas (NHLs) and 126 healthy individuals were genotyped using the PCR-VNTR technique. A slightly higher frequency of the MNS16A VNTR-243 variant was detected among patients who did not respond to treatment (NR) as compared to patients with complete or partial remission (0.83 vs. 0.51, P = 0.055). NR patients more frequently developed aggressive than indolent type of the disease (0.92 vs. 0.41, P = 0.001). The VNTR-243 allele was more frequently detected among patients with an intermediate-high/high International Prognostic Index (IPI 3-4) score (P = 0.063), especially in patients with advanced age and IPI 3-4 (P = 0.040). In multivariate analysis, higher IPI 3-4 score (OR = 11.364, P = 0.051) and aggressive type of the disease (OR = 18.182, P = 0.012) were found to be independent genetic markers associated with nonresponse to treatment. Presence of the MNS16A VNTR-243 variant also strongly tended to affect the risk of a less favourable response to therapy and was more frequently present among nonresponders (OR = 5.848, P = 0.059). Genetic variation within the hTERT gene may affect the progression and treatment of lymphoproliferative disorders.