Expression of HERV-K and embryonic genes in chronic lymphocytic leukemia and their association with therapy regimens

慢性淋巴细胞白血病中 HERV-K 和胚胎基因的表达及其与治疗方案的关系

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Abstract

Dysregulated expression of human endogenous retrovirus K (HERV-K) has been found in many types of tumors. Previously, we demonstrated the concomitant expression of HERVs and embryonic genes in cancer cells with aggressive and stemness features. In the field of onco-hematology, some studies have described alterations of HERV expression in chronic lymphocytic leukemia (CLL), the most common adult leukemia in the Western world. Despite numerous achievements in CLL clinical research, given the heterogeneity of the disease and the different treatment choices, identification of new biomarkers for patient management is needed. On this basis, this work aimed to evaluate the expression of HERVs and embryonic genes as novel combined biomarkers in CLL and their potential association with clinical features and therapy regimens. Peripheral blood mononuclear cells were isolated from 49 healthy donors (HDs) and 74 patients with CLL, evaluating their treatment regimen. The expression of different HERVs and embryonic genes was analyzed by real-time polymerase chain reaction. Molecular analysis showed higher expression of HERVs and embryonic genes in patients than HDs, differently expressed according to treatment status. Using principal component analysis, we found complex expression profiles of HERVs and embryonic genes associated with CLL and different treatment regimens. In ibrutinib-treated patients, HERVs were found to be associated with unfavorable prognostic factors of CLL. These findings, although requiring confirmation in larger patient cohorts, highlight the interconnection between HERVs and embryonic genes in CLL, suggesting their use as potential new biomarkers in monitoring innovative treatments.

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