Abstract：
Relapsed or refractory diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) patients still faced with poor survival, representing an unmet clinical need. In-depth research into the disease\'s pathogenesis and the development of targeted treatment strategies are urgently needed. Here, we conducted a comprehensive bioinformatic analysis of gene mutation and expression using data from our center and public databases. Cell cycle-related genes especially for CDKN2A/B-CDK4/6/CCND1 machinery altered frequently in DLBCL and MCL. Clinically, high CDK4 and CDK6 expression were correlated with poor prognosis of DLBCL and MCL patients. Furthermore, we also validated the pharmacological efficacy of CDK4/6 inhibitor palbociclib and its synergy effect with PI3K inhibitor idelalisib utilizing in vitro cell lines and in vivo cell-derived xenograft (CDX) and patient-derived xenograft (PDX) mouse models. Our results provided sufficient pre-clinical evidence to support the potential combination of palbociclib and idelalisib for DLBCL and MCL patients.
摘要：
复发或难治性弥漫性大B细胞淋巴瘤（DLBCL）和套细胞淋巴瘤（MCL）患者仍然面临生存不良，代表未满足的临床需求。迫切需要深入研究该病的发病机制,制定针对性的治疗策略。这里,我们利用中心和公共数据库的数据对基因突变和表达进行了全面的生物信息学分析.细胞周期相关基因，特别是CDKN2A/B-CDK4/6/CCND1机制在DLBCL和MCL中经常改变。临床上,CDK4和CDK6高表达与DLBCL和MCL患者的不良预后相关。此外，我们还利用体外细胞系和体内细胞源性异种移植(CDX)和患者源性异种移植(PDX)小鼠模型,验证了CDK4/6抑制剂palbociclib的药理作用及其与PI3K抑制剂idelalisib的协同作用.我们的结果提供了足够的临床前证据来支持Palbociclib和idelalisib用于DLBCL和MCL患者的潜在组合。
