Immune System Development and Function Program, Centro Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Departamento de Hematología, Hospital Universitario de Salamanca (HUS-IBSAL), 37007 Salamanca, Spain.
Cells. 2023 Nov 22;12(23):2687. doi: 10.3390/cells12232687.
Chronic lymphocytic leukemia (CLL) is a hematologic malignancy characterized by progressive accumulation of a rare population of CD5+ B-lymphocytes in peripheral blood, bone marrow, and lymphoid tissues. CLL exhibits remarkable clinical heterogeneity, with some patients presenting with indolent disease and others progressing rapidly to aggressive CLL. The significant heterogeneity of CLL underscores the importance of identifying novel prognostic markers. Recently, the RAS-related gene has emerged as both a driver oncogene and a potential marker for CLL progression, with higher expression associated with poorer disease prognosis. Although missense somatic mutations in the coding sequence of have not been described in CLL, this study reports the frequent detection of three somatic mutations in the 3' untranslated region (3'UTR) affecting positions +26, +53, and +180 downstream of the stop codon in the mRNA. An inverse relationship was observed between these three somatic mutations and mRNA expression, which correlated with lower blood lymphocytosis. These findings highlight the importance of overexpression in CLL development and prognosis and point to somatic mutations in its 3'UTR as novel mechanistic clues. Our results may contribute to the development of targeted therapeutic strategies and improved risk stratification for CLL patients.
慢性淋巴细胞白血病（CLL）是一种血液恶性肿瘤，其特征是外周血、骨髓和淋巴组织中罕见的 CD5+B 淋巴细胞的进行性积累。CLL 表现出显著的临床异质性，一些患者表现为惰性疾病，而另一些患者则迅速进展为侵袭性 CLL。CLL 的显著异质性突出表明需要识别新的预后标志物。最近，RAS 相关基因 已成为 CLL 进展的驱动癌基因和潜在标志物，较高的 表达与较差的疾病预后相关。尽管在 CLL 中尚未描述编码序列中的 错义体细胞突变，但本研究报告了频繁检测到三个影响 mRNA 终止密码子下游 +26、+53 和 +180 位置的 3'非翻译区（3'UTR）中的体细胞突变。这三个体细胞突变与 mRNA 表达呈负相关，与血液淋巴细胞增多症相关。这些发现强调了 过表达在 CLL 发展和预后中的重要性，并指出其 3'UTR 中的体细胞突变是新的机制线索。我们的研究结果可能有助于开发针对 CLL 患者的靶向治疗策略和改善风险分层。
