IL-35 and IL-18 Serum Levels in Children With Acute Lymphoblastic Leukemia: The Relationship With Prognostic Factors.

Acute lymphoblastic leukemia (ALL) is the most common type of cancer among children. In this study, we investigated the serum levels of interleukin (IL)-35 and IL-18 in children with ALL to compare with healthy subjects and find their relationship with prognostic factors and response to therapy. IL-35 and IL-18 serum concentrations in 40 children diagnosed with ALL and 35 age-matched and sex-matched healthy children were measured using ELISA. The association between cytokine levels and patients' clinical and laboratory data were determined. A significant difference was found in IL-35 serum levels between the patients (3.6±1.5 ng/mL) and controls (2.5±1.8 ng/mL) (P=0.007). No significant difference in IL-18 serum levels between these groups was observed. A positive correlation between IL-35 and IL-18 levels was detected (P=0.001). The authors found that patients with lower platelet count had higher IL-35 concentration (P=0.003). By considering a cut-off value of 6.21 ng/mL (mean±2SD of controls) for IL-35, it was found that white blood cell (WBC) count was higher in patients with IL-35 >6.21 ng/mL (P=0.016), and the majority of these patients had T-ALL (P=0.01). Although the mean overall survival in patients with IL-35 >6.21 ng/mL was shorter (937±381 d) than in those with IL-35 ≤6.21 ng/mL (1567±103 d), but the result was not significant (P=0.1, log-rank test). The IL-18 level was associated with a lower hemoglobin level (P=0.027). These data suggested a role for IL-35 in ALL development. The significant relation of IL-35 to white blood cells and platelet counts may imply a possible influence of IL-35 on ALL prognosis.

Association of IL-27 rs153109 and rs17855750 Polymorphisms with Risk and Response to Therapy in Acute Lymphoblastic Leukemia.

Interleukin (IL)-27 is a cytokine with important anti-cancer activity. This study has evaluated the effects of IL-27 rs153109 and rs17855750 single nucleotide polymorphisms (SNPs) on risk of acute lymphoblastic leukemia (ALL) development, as well as their impact on prognosis and patient survival. A total of 200 patients and 210 healthy subjects were genotyped by polymerase chain reaction-restriction fragment length polymorphism. We observed a higher frequency of rs153109 AG and rs17855750 TG genotypes and allele G in patients compared to controls (p < 0.001). Combined G variant genotypes (AG + GG and TG + GG) also conferred significantly greater risk of ALL. There was a significant correlation between the genotypes of both SNPs with event-free survival (EFS). Patients with GG genotypes of both SNPs and those of rs153109 AG and rs17855750 TG had a shorter EFS than patients with rs153109 AA and rs17855750 TT genotypes (p ≤ 0.035). Combined G variant genotypes for both SNPs showed poorer response to therapy in all patients (p < 0.027) as well as B-ALL (rs153109, p < 0.001) and T-ALL (rs153109, p = 0.048) patients. In multivariate analysis, rs153109 combined G variant genotype was associated with shorter EFS (relative risk = 9.7, p = 0.026). Among those who relapsed, 87.1% had the rs153109 AG genotype and 77.4% had the rs17855750 TG genotype (p < 0.01). Patients had higher IL-27 serum levels compared to controls, but this did not differ between genotypes. In conclusion, the association of IL-27 rs153109 and rs17855750 polymorphisms with risk of ALL development and their impact on EFS suggested an important role for this cytokine in biology and response to ALL therapy.