Matteucci Claudia, Petrone Vita, Giovinazzo Alessandro, Laureana Roberta, Postorino Massimiliano, Pupo Livio, Cipriani Chiara, Toschi Nicola, Fanelli Marialaura, Minutolo Antonella, Paterno Giovangiacinto, Buzzatti Elisa, Sinibaldi Vallebona Paola, Zucchetto Antonella, Pozzo Federico, Gattei Valter, Del Poeta Giovanni, Venditti Adriano, Balestrieri Emanuela, Del Principe Maria Ilaria
Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy.
Institute of Biochemistry and Cell Biology, Consiglio Nazionale delle Ricerche Monterotondo, Rome, Italy.
Blood Adv. 2025 Aug 26;9(16):4265-4278. doi: 10.1182/bloodadvances.2024014181.
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.
在多种类型的肿瘤中都发现了人类内源性逆转录病毒K（HERV-K）的表达失调。此前，我们证明了具有侵袭性和干性特征的癌细胞中HERV与胚胎基因的共表达。在肿瘤血液学领域，一些研究描述了慢性淋巴细胞白血病（CLL）中HERV表达的改变，CLL是西方世界最常见的成人白血病。尽管CLL临床研究取得了众多成果，但鉴于该疾病的异质性和不同的治疗选择，仍需要识别新的生物标志物用于患者管理。在此基础上，本研究旨在评估HERV和胚胎基因作为CLL新型联合生物标志物的表达及其与临床特征和治疗方案的潜在关联。从49名健康供体（HD）和74名CLL患者中分离外周血单个核细胞，并评估他们的治疗方案。通过实时聚合酶链反应分析不同HERV和胚胎基因的表达。分子分析显示，患者中HERV和胚胎基因的表达高于HD，且根据治疗状态表达不同。使用主成分分析，我们发现了与CLL和不同治疗方案相关的HERV和胚胎基因的复杂表达谱。在接受依鲁替尼治疗的患者中，发现HERV与CLL的不良预后因素相关。这些发现尽管需要在更大的患者队列中得到证实，但突出了CLL中HERV与胚胎基因之间的相互联系，表明它们可作为监测创新治疗的潜在新生物标志物。
