Interleukin-4 gene intron 3 VNTR polymorphism in adult acute myeloid leukemia

Abstract

Background The proliferation of acute myeloid leukemia (AML) blast into the bone marrow microenvironment is controlled by cytokines. Interleukin-4 (IL-4) has recently been discovered to suppress the development and persistence of AML cells selectively. Intron three of the Interleukin-4 (IL-4) gene contains a 70-bp minisatellite region polymorphism that may influence gene transcriptional activity and subsequently affect the production level of IL4. We investigated the IL-4 gene intron three variable number tandem repeat (VNTR) polymorphism as a molecular marker in AML associated with clinical and laboratory variables and a prognostic factor for therapeutic response and disease outcome. Results IL-4 gene intron three minisatellite regions polymorphism was assessed in 60 adult AML patients and 60 healthy controls, comparable concerning age and gender, using polymerase chain reaction. Three study marker genotypes were detected in AML patients; P1/P1 (3%), P1/P2 (40%), and P2/P2 (56.7%). The frequency of P2 alleles was significantly more in AML patients than in healthy controls (76.7% versus 25%; P < 0.001). Compared to the heterozygous group and P1/P1 carriers, AML patients with the homozygous P2/P2 genotype had a higher total leucocytic count and increased blast percentages in bone marrow or peripheral blood, besides a lower platelet count. P2P2 genotype was also significantly associated with poor therapeutic response, higher susceptibility to disease recurrence and shorter overall survival and disease-free survival. Conclusion The IL-4 intron 3 VNTR polymorphism could be included in the molecular risk stratification of AML to predict poor disease. This information can be utilized in incorporating biological therapy into the present therapeutic protocols to enhance chemotherapy regimens’ current low response rates.

Detection of IL-1β, VEGF and IL-4 with their novel genetic variations in breast cancer patients

“…These results provide an interpretation for the decreased level of IL-4 in BC. Moreover, several polymorphisms related to IL-4 encoding gene were shown to be a cancer risk factor ( Ibrahimi et al, 2018 , Shabbir et al, 2022 , Safwat et al, 2022 ).…”

Predictive value of KRAS/NRAS, IL-4 VNTR and HPV alterations in metastases of colorectal cancer

“…Concertedly with previous studies, 3R/3R genotype of IL-4 VNTR was proven as a protective factor against breast cancer susceptibility in an Iranian population (30) while the effect of IL-4 VNTR variants was not observed in Jordanian breast cancer patients (31). In adult acute myeloid leukemia patients, the frequency of 3R alleles was higher than in controls and 3R/3R genotype was reported to be signifi cantly associated with poor therapeutic response, higher susceptibility to disease recurrence and shorter overall survival and disease-free survival (32). This result was in contradiction with the study of Ahmed et al (33) who reported 2R/2R and 2R/3R genotypes as high risk factors for the development of leukemia.…”