套细胞淋巴瘤
伊布替尼
替西罗莫司
肿瘤科
内科学
胚泡
国际预后指标
医学
队列
血液学
脾边缘带淋巴瘤
CDKN2A
淋巴瘤
基因表达谱
临床试验
癌症研究
生物
生物信息学
弥漫性大B细胞淋巴瘤
白血病
基因
基因表达
遗传学
癌症
慢性淋巴细胞白血病
mTOR抑制剂的发现与发展
脾切除术
细胞凋亡
蛋白激酶B
脾脏
作者
Ciara L. Freeman,Prasath Pararajalingam,Ling Jin,Sriram Balasubramanian,Aixiang Jiang,Wendan Xu,Michael Grau,Myroslav Zapukhlyak,Merrill Boyle,Brendan P. Hodkinson,Michael Schäffer,Christopher Enny,Sanjay Deshpande,Steven Sun,Jessica Vermeulen,Ryan D. Morin,David W. Scott,Georg Lenz
出处
期刊:Leukemia
[Springer Nature]
日期:2022-08-13
卷期号:36 (10): 2479-2487
被引量:6
标识
DOI:10.1038/s41375-022-01658-2
摘要
Mantle cell lymphoma (MCL) is a rare, incurable lymphoma subtype characterized by heterogeneous outcomes. To better understand the clinical behavior and response to treatment, predictive biomarkers are needed. Using residual archived material from patients enrolled in the MCL3001 (RAY) study, we performed detailed analyses of gene expression and targeted genetic sequencing. This phase III clinical trial randomized patients with relapsed or refractory MCL to treatment with either ibrutinib or temsirolimus. We confirmed the prognostic capability of the gene expression proliferation assay MCL35 in this cohort treated with novel agents; it outperformed the simplified MCL International Prognostic Index in discriminating patients with different outcomes. Regardless of treatment arm, our data demonstrated that this assay captures the risk conferred by known biological factors, including increased MYC expression, blastoid morphology, aberrations of TP53, and truncated CCND1 3' untranslated region. We showed the negative impact of BIRC3 mutations/deletions on outcomes in this cohort and identified that deletion of chromosome 8p23.3 also negatively impacts survival. Restricted to patients with deletions/alterations in TP53, ibrutinib appeared to abrogate the deleterious impact on outcome. These data illustrate the potential to perform a molecular analysis of predictive biomarkers on routine patient samples that can meaningfully inform clinical practice.
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