ORIGINAL ARTICLE Tumor necrosis factor-α (TNF-α) -308 G/A and lymphotoxin-α (LT-α) +252 A/G genetic polymorphisms in Egyptian acute lymphoblastic leukemia Sherin M. Abd El-Aziz 1 & Wael Alkhiary 1 & Naglaa Mokhtar 2 & Mona Talaab 3 Received: 31 March 2017 /Accepted: 7 November 2017 # Springer-Verlag London Ltd., part of Springer Nature 2017 Abstract Acute lymphoblastic leukemia (ALL) is one of the most hematological malignancies of lymphoid origin. It has been proposed that deregulation of cytokines could be linked with pathogenesis, progression, and survival in many dis- eases. Genetic polymorphisms in two important cytokines like tumor necrosis factor-α (TNF-α) -308 and lymphotoxin-α (LT-α) +252 can disturb both their transcription and expres- sion and lead to their high plasma levels. A difference in the occurrence of the polymorphisms in TNF-α -308 G/A and LT-α +252 A/G in ALL cases among several populations with different ethnicities was observed. The study investigated the occurrence and the role of polymorphisms of tumor necrosis factor genes including TNF-α -308 G>A and LT-α +252 A>G in the development of ALL in Egypt. A case-control study was done on 126 newly diagnosed ALL patients (96 pediatric and 30 adult patients); 130 healthy subjects com- posed the control group. Polymorphism variants of TNF-α and LT-α genes were studied by PCR-RFLP on genomic DNA of all studied individuals. TNF-α -308 G/A polymor- phism was statistically significant in ALL pediatric patients (P value = 0.008) with no association with ALL adult patients. TNF AA homozygous variant genotype and the A allele both showed significant risks of the development of pediatric ALL. However, there was no association between LT-α +252 A/G polymorphism in both pediatric and adult ALL. The results show that TNF AA homozygous variant genotype and A allele showed a significant risk of development of pediatric ALL. Keywords Acute lymphoblastic leukemia . TNF-α -308 G>A . LT-α +252 A>G . Polymorphisms Introduction Acute lymphoblastic leukemia (ALL) occurs in both children and adults, yet its incidence peaks between 2 and 5 years of age (Inaba et al. 2013; Ofran and Rowe 2014), being the most common childhood cancers (Lacour and Clavel 2014). The complex etiology of ALL has not been fully elucidated. While the roles of some environmental factors have been questioned as potential risk factors (Zuckerman and Rowe 2014; Bhojwani et al. 2015), cumulative evidence suggests that genetic factors may play a significant role in the patho- genesis of ALL (Mullighan 2013; Mullighan 2012; Urayama and Manabe 2014). The tumor necrosis factor (TNF) superfamily is a family of cytokines capable of causing cellular apoptosis. Tumor necro- sis factor alpha (TNF-α) is a pleiotropic pro-inflammatory cytokine secreted mainly by T-helper lymphocytes (Th-1, CD4+). Lymphotoxin-α (LT-α; formerly TNF-β) is produced mainly by mitogen-stimulated T lymphocytes and leukocytes (Šedý et al. 2014; Fulda 2014). Both are recognized for their ability to activate the normal development of B cells, and they are potent controllers of both B and T lymphocytes, by sig- naling via TNF receptors (Figgett et al. 2014; Rickert et al. 2011). * Sherin M. Abd El-Aziz sherin_abdaziz@yahoo.com 1 Hematology Unit, Clinical pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt 2 Medical Biochemistry Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt 3 Clinical Hematology Unit, Faculty of Medicine, Mansoura University, Mansoura, Egypt Comp Clin Pathol https://doi.org/10.1007/s00580-017-2600-6