Tsagiopoulou M, Rashmi S, Chatziaslani M, Gut I
Centro Nacional de Analisis Genomico (CNAG), Barcelona, Spain.
Aristotle University of Thessaloniki (AUTh), Thessaloniki, Greece.
Front Pharmacol. 2025 Aug 15;16:1642458. doi: 10.3389/fphar.2025.1642458. eCollection 2025.
Chronic Lymphocytic Leukemia (CLL) is characterized by clinical and biological heterogeneity, with a subset of patients progressing to Richter Transformation (RT), an aggressive lymphoma. This study explores MYC target gene activation across various CLL stages and disease subgroups using bulk RNAseq and single-cell RNAseq data. Our findings reveal increased MYC activation in unmutated IGHV CLLs, trisomy 12 cases, and RT stages. In RT, MYC activation is independent of B-cell receptor signaling, correlating instead with cell cycling and TLR9 interactions, indicating alternative survival mechanisms. High MYC activation correlates with shorter time to first treatment and enhances tumor microenvironment interactions, particularly with myeloid cells. These results underscore MYC's significant role in CLL progression and RT, supporting MYC's potential as a target for stratifying CLL patients and developing therapeutic strategies.
慢性淋巴细胞白血病（CLL）具有临床和生物学异质性，一部分患者会进展为Richter转化（RT），这是一种侵袭性淋巴瘤。本研究使用批量RNA测序和单细胞RNA测序数据，探索了MYC靶基因在不同CLL阶段和疾病亚组中的激活情况。我们的研究结果显示，未突变IGHV的CLL、三体12病例以及RT阶段中MYC激活增加。在RT中，MYC激活独立于B细胞受体信号传导，而是与细胞周期和TLR9相互作用相关，表明存在其他生存机制。高MYC激活与首次治疗时间缩短相关，并增强肿瘤微环境相互作用，特别是与髓样细胞的相互作用。这些结果强调了MYC在CLL进展和RT中的重要作用，支持MYC作为分层CLL患者和制定治疗策略靶点的潜力。
