威尼斯人
多发性骨髓瘤
癌症研究
外显子组测序
外显子组
基因表达谱
基因组
来那度胺
医学
生物
癌症的体细胞进化
全基因组测序
硼替佐米
突变
基因组学
基因缺失
无进展生存期
基因组不稳定性
基因
Carfilzomib公司
抗药性
肿瘤科
总体生存率
生物信息学
髓样
转录组
生存分析
表型
淋巴瘤
遗传学
后天抵抗
临床试验
选择(遗传算法)
免疫学
基因组测序
合成致死
作者
Marcella Kaddoura,Julia Erin Wiedmeier-Nutor,Vikas A. Gupta,Tomas Jelinek,Bachisio Ziccheddu,Suganti Shivaram,Hongwei Tang,Rebecca W Owens,Ševčíková Tereza,R. Fonseca,Michael Durante,Benjamin Diamond,Logan Zhao,Yuan Xiao Zhu,Chang-Xin Shi,Shannon M. Matulis,C. Mitsiades,Ola Landgren,Saad Z. Usmani,R Hajek
出处
期刊:Blood
[Elsevier BV]
日期:2026-01-02
标识
DOI:10.1182/blood.2025029996
摘要
Multiple myeloma (MM) with t(11;14)(CCND1;IGH) remains the only subset sensitive to the BCL2 inhibitor venetoclax. Not all t(11;14)(CCND1;IGH) patients respond to treatment and some progress early after initial response. To investigate this, we interrogated 44 whole genome and exome sequencing data from 34 patients with t(11;14) MM treated with venetoclax. The presence of mutations in the RAS pathway was strongly associated with shortened progression-free survival (PFS) and was validated in an independent cohort of 21 MM patients. Presence of 1q gain was also associated with shorter PFS in patients without RAS mutations. In 10 patients with paired, pre- and post-venetoclax treatment samples, post-venetoclax progression was recurrently driven by the selection of genomic events in BCL2/MCL1 and RAS pathways and of high-risk features (e.g., loss of TP53 and CDKN2C). Overall, our study shows that comprehensive genomic profiling can identify most mechanisms underlying resistance to BCL2 inhibition in t(11;14)(CCND1;IGH) MM.
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