TGFΒ 2 RS79375991 GENE POLYMORPHISM IN IRAQI CHRONIC MYELOID LEUKEMIA PATIENTS INFECTIOUS WITH HUMAN HERPES VIRUS-8

Abstract

Abstract

Background: HHV8 + primary effusion lymphoma (PEL), EB-LBCL has no known association with HIV or HHV8 infection. Plural or pericardial effusions complicate BCR::ABL1-positive (CML) in around one-third of patients. According to recent findings, the maintenance of cancer stem cells is influenced by transforming growth factor-β (TGF-β) in both positive and negative ways, depending on the kind of cell and the setting. Currently, little is understood about the relationship between Bcr-Abl expression and TGFbeta and downstream Smad transcription factors and CML cell growth.

Objective: cross-sectional case-control study was aimed to determine the association between TGFβ 2 rs79375991 polymorphism; BCR protein level; biochemical parameters and the percentage of HHV-8 in patients with CML.

Patients and methods: A cross-sectional case-control study included one tow hundred (200) blood specimens enrolled in the current research, including 120 CML (20 patients diagnosed as newly diagnosed; 100 patients treated CML 65 out of 100 patients on imatinib while 35 were treated with other tyrosine kinase inhibitors (Nilotinib and Bosutinib); as well as eighty (80) blood specimens collected from persons as apparently healthy control group were aged 16 to 65 years. Conventional PCR was chosen for the DNA- HHV-8 detection as well as TGFβ 2 rs79375991 gene polymorphism by sequencing. Lastly, ELISA used serum to detect the BCR protein level among studied groups.

Results: The current study included 20 patients diagnosed as newly diagnosed CML with mean age 35±12 years and 100 patients treated CML with mean age 51±11.89 years. While, mean age of apparently healthy-looking persons 44±13.7 years. There are statistically differences between new diagnosis CML group and controls group in serum level of (Urea, Creatinine, ALT, AST and LDH), p-value (0.004, 0.014, <0.001, <0.001 <0.001), respectively. The positive result of HHV-8 according to PCR shows 49.3 % (33 out of 67 cases) as positive, while 50.7% (34 out of 67 cases) as negative,. While, not found positive of HHV-8 infection in all examined apparently healthy specimens. HHV-8-PCR detection results from patients with various forms of CML were 3.3%, 16.7%, and 25.8% of new diagnosis CML, patients respond to treatments and relapse groups, respectively, showed positive PCR results for HHV-8 detection. The results of TGFβ 2 rs79375991 gene polymorphism showed difference in frequency of genotype distribution of the polymorphism between patients and controls groups was statistically significant. According to BCR protein level, there are highly statistically significant differences between new diagnosis group and response to treatment group, while non-significant differences between respond to treatment and relapse group (p-value: 0.64).

Conclusion: The significant correlation between the gene polymorphism of TGFβ 2 rs79375991; BCR protein with HHV-8 infection could indicate highly important role of these molecular factors in patients suffering from CML.