Introduction: Chronic myeloid leukemia (CML) is a myeloproliferative malignancy driven by the BCR::ABL1 fusion gene that results in uncontrolled expansion of haematopoietic stem cells. Stylistic response: An emerging body of knowledge indicates that in addition to host genetic factors _ contribute to disease progression. Human herpesvirus-8 (HHV-8) has been associated with some hematological neoplasia, whereas polymorphisms of the CARD8 gene can regulate inflammation pathways and cancer progress. We have examined the relationship between HHV-8 infection and CARD8 polymorphism in Iraqi patients with CML. Materials and methods The present study was a 120-case, 1:4, cross-sectional case-control study conducted on 120 patients who were diagnosed with CML (20 newly diagnosed; 100 treated) with 80 apparently healthy controls. All participants provided blood samples. Polymerase chain reaction (PCR) was applied for HHV-8 DNA detection, and molecular genetic methods were used for CARD8 gene polymorphisms analysis. Biochemical parameters (urea, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and BCR PP levels) were also analyzed. Statistical analyses were conducted to evaluate between-group differences or associations Emerging data implicate viral infection and genetic determinants of the host in disease progression. Human herpesvirus-8 (HHV-8) infection has been involved in several hematological malignancies and differences in CARD8 polymorphisms can influence the inflammatory pathways and influence tumor development. This study was this investigation of infection with HHV-8 and the gene polymorphism of the CARD8 gene in Iraqi patients with cML. Materials and methods: A Cross sectional case-control study on 120 CML cases include 20 newly diagnosed and 100 treated cases along with 80 apparently healthy controls. All participants provided blood samples. Polymerase chain reaction (PCR) was used to detect HHV-8 DNA and CARD8 gene polymorphisms were examined through molecular genetics. Biochemical parameters such as urea, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and BCR protein levels were also measured. All statistical analyses were conducted to assess differences between the groups and to ascertain any possible associations. Results: HHV-8 DNA was positive in 49.3% of CML patients examined but negative in all donor-type controls. The maximum HHV-8 infection rate was seen in the 51–60 year age group patients (table 2). The distribution of CARD8 genotype between patients and controls was significant, implying an association between CARD8 polymorphism and CML susceptibility. Biochemical parameters such as ALT, AST, LDH, urea and creatinine also showed large differences across patients compared to controls. Furthermore, HHV-8 infection matched a strong positive correlation with CARD8 polymorphism in CML patients. Levels of BCR protein were considerably lower in newly diagnosed patients than in treatment responders; thus, BCR protein can be used as a marker of disease activity. Discussion: These results indicate that the HHV-8 infection can play a co-factor in the pathogenesis and progression of the CML among Iraqi patients. In addition, CARD8 gene polymorphism seems to increase the suscptibility to CML and may contribute to the biology of the disease via inflammatory and immune regulatory pathways. The strong association between HHV-8 infection and CARD8 polymorphism also suggests an interplay between viral and genetic factors in CML development. These results reveal new aspects of CML pathobiology that may assist in discovering novel biomarkers for the diagnosis, prognosis, and monitoring of the disease.
