Supplement: Large scale single-cell gene rearrangement detection with a microfluidic device

补充：利用微流控装置进行大规模单细胞基因重排检测

• 批准号: 10522287
• 负责人: John Zhong
• 金额: $ 26.35万
• 依托单位: LOMA LINDA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10522287
• 关键词: Acute Myelocytic Leukemia; Alternative Splicing; Cells; Chromosome abnormality; Clinical; Cytogenetics; Detection; Diagnosis; Gene Rearrangement; Leukemic Cell; Malignant Neoplasms; Messenger RNA; Microfluidic Microchips; Molecular; Names; Resolution; Selection for Treatments; Spliced Genes; Techniques; adult leukemia; base; fusion gene; leukemia treatment; risk stratification; single-cell RNA sequencing; translational goal

Acute myeloid leukemia (AML) contributes to 32% of all adult leukemia and remains one of the most clinically devastating cancers. Currently, AML diagnosis, risk stratification and treatment selection are mainly based on cytogenetic abnormalities, which suffers from low sensitivity and low resolution. To overcome this technical hurdle, we propose to use single-cell RNAseq with microfluidic devices to generate a molecular version of AML cytogenetic profile including all mRNA abnormalities from a large number of leukemia cells, a technique we have named S-CytoSeq. This molecular S- CytoSeq profiling provides fusion genes (FG) and alternative splicing (AS) profiles at single-cell resolution and will have a significant clinical impact on AML treatment. The ultimate translational goal is to replace conventional cytogenetics with S-CytoSeq.

急性髓系白血病(AML)占成人白血病的32%， 仍然是临床上最具破坏性的癌症之一。目前，AML诊断、风险 分层和治疗选择主要基于细胞遗传学异常， 它具有低灵敏度和低分辨率的缺点。为了克服这一技术障碍， 我们建议使用带有微流控装置的单细胞RNAseq来产生分子 AML细胞遗传学图谱的版本，包括来自大的 白血病细胞的数量，我们将这项技术命名为S细胞序列。这个分子S- CytoSeq图谱提供融合基因(FG)和选择性剪接(AS)图谱 并将对急性髓细胞白血病的治疗产生重大的临床影响。这个 翻译的最终目标是用S-细胞序列取代传统的细胞遗传学。