Transcriptome analysis of primary adult B-cell lineage acute lymphoblastic leukemia identifies pathogenic variants and gene fusions, and predicts subtypes for in depth molecular diagnosis.
Transcriptome analysis of primary adult B-cell lineage acute lymphoblastic leukemia identifies pathogenic variants and gene fusions, and predicts subtypes for in depth molecular diagnosis.
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原发性成人 B 细胞谱系急性淋巴细胞白血病的转录组分析可识别致病变异和基因融合，并预测亚型以进行深入的分子诊断。
DOI：
10.1111/ejh.14164
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发表时间：
2024
影响因子：
3.1
通讯作者：
Schjerven,Hilde
中科院分区：
文献类型：
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作者：
Podgorica,Mirjam;Drivet,Elsa;Viken,JonasKrag;Richman,Alyssa;Vestbøstad,Johanne;Szodoray,Peter;Kvam,AnnKristin;Wik,HildeSkuterud;Tjønnfjord,GeirE;Munthe,LudvigA;Frietze,Seth;Schjerven,Hilde
背景B细胞急性淋巴细胞白血病（B-ALL）根据已知的驱动癌基因和分子病变（包括易位和复发突变）分为亚组。然而，目前的诊断测试不确定亚型或致癌病变的所有B-ALL样本，创建一个异质性B-ALL组的未知subtype.MethodsWe分类的主要成人B-ALL细胞，并进行转录组分析批量RNA测序（RNA-seq）.ResultsTranscriptomic分析的成人B-ALL队列允许分类的4个患者样本的亚型，以前没有透露标准基因面板。2例患者的白血病为DUX 4亚型，2例为CRLF 2 +Ph‐样B‐ALL。此外，单核苷酸变异分析在3个患者样本中检测到致癌NRAS-G12 D、KRAS-G12 D和KRAS-G13 D突变，呈现靶向突变。额外的致癌变异和基因融合被发现，以及在五个病人samples.ConclusionWe的PDE 4 DIP基因的多个变体证明，RNA测序是一个有效的工具，精确医学在B-ALL通过提供全面的白血病细胞的分子分析，确定亚型和致癌病变，并分层患者进行适当的治疗。
BackgroundB‐cell acute lymphoblastic leukemia (B‐ALL) is classified into subgroups based on known driver oncogenes and molecular lesions, including translocations and recurrent mutations. However, the current diagnostic tests do not identify subtypes or oncogenic lesions for all B‐ALL samples, creating a heterogeneous B‐ALL group of unknown subtypes.MethodsWe sorted primary adult B‐ALL cells and performed transcriptome analysis by bulk RNA sequencing (RNA‐seq).ResultsTranscriptomic analysis of an adult B‐ALL cohort allowed the classification of four patient samples with subtypes that were not previously revealed by standard gene panels. The leukemia of two patients were of the DUX4 subtype and two were CRLF2+Ph‐like B‐ALL. Furthermore, single nucleotide variant analysis detected the oncogenic NRAS‐G12D, KRAS‐G12D, and KRAS‐G13D mutations in three of the patient samples, presenting targetable mutations. Additional oncogenic variants and gene fusions were uncovered, as well as multiple variants in thePDE4DIPgene across five of the patient samples.ConclusionWe demonstrate that RNA‐seq is an effective tool for precision medicine in B‐ALL by providing comprehensive molecular profiling of leukemia cells, identifying subtype and oncogenic lesions, and stratifying patients for appropriate therapy.