Polymorphism of Interleukins and Tumor Necrosis Factor α Genes in Multiple Myeloma Patients with Autologous Hematopoietic Stem Cell Transplantation

SP Svitina, ZhYu Sidorova, II Kostroma, AA Zhernyakova, AV Chechetkin, ZhV Chubukina, SV Gritsaev, SI Kapustin, SS Bessmeltsev

Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: Svetlana Pavlovna Svitina, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; e-mail: shvetikova@gmail.com

For citation: Svitina SP, Sidorova ZhYu, Kostroma II, et al. Polymorphism of Interleukins and Tumor Necrosis Factor α Genes in Multiple Myeloma Patients with Autologous Hematopoietic Stem Cell Transplantation. Clinical oncohematology. 2021;14(3):340–6. (In Russ).

DOI: 10.21320/2500-2139-2021-14-3-340-346


ABSTRACT

Aim. To assess polymorphism value of interleukins (IL6, IL1B, IL10) and tumor necrosis factor α (TNF) genes in multiple myeloma (MM) patients who received autologous hematopoietic stem cell transplantation (auto-HSCT).

Materials & Methods. The study enrolled 37 MM patients (15 men and 22 women) aged 38–66 years (mean age 54.5 ± 6.4 years), who received auto-HSCT. After transplantation, partial (PR), very good partial (VGPR), and complete (CR) responses were reported in 11, 7, and 19 patients, respectively. In 23 (62.2 %) patients CD34+ cell collection on the day of the first leukocytapheresis session exceeded the suboptimal level of 2.5 × 106/kg. The control group included 236 healthy subjects. Genotyping by PCR with subsequent analysis of restriction fragment length polymorphism of amplified products was performed. To identify between-group differences in genotype distribution, Fisher’s exact test with measurements of odds ratio (OR) and рvalue was used.

Results. The study group of patients was distinguished from the control group by more than twofold increased proportion of homozygous IL1B –31C (OR 2.7; = 0.029). The proportion of heterozygous –174G/C allelic variant of IL6 gene in the subgroup of patients with CR after auto-HSCT was considerably higher than in patients with VGPR and PR (OR 5.6; = 0.022). In the subgroup of patients with CD34+ cell collection > 2.5 × 106/kg the proportion of those with IL10 –592C/C genotype was twice as high as in patients with lower CD34+ cell collection (OR 3.9; = 0.091).

Conclusion. The present study confirms the relationship of –31C/Т polymorphism in IL1B gene in homozygous state with higher MM risk. It proved the association of –174G/C polymorphism in IL6 gene and –592C/A polymorphism in IL10 gene with the chosen criteria for auto-HSCT efficacy. To precisely clarify the value of variants in the above genes for predicting chemotherapy effect in MM, further studies involving more patients are required.

Keywords: multiple myeloma, genes polymorphism, immune response, cytokines, autologous hematopoietic stem cell transplantation.

Received: March 4, 2021

Accepted: June 10, 2021

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