Multiple myeloma (MM) is the second most common hematological malignancy. Approximately 15% of MM patients are affected by the t(4;14) translocation resulting in theIGH::NSD2fusion transcript. Breakage occurs in three major breakpoint regions within theNSD2gene (MB4-1, MB4-2, and MB4-3), where MB4-1 leads to the production of full-length protein, while truncated proteins are expressed in the other two cases. Measurable residual disease (MRD) has been conclusively established as a crucial prognostic factor in MM. TheIGH::NSD2fusion transcript can serve as a sensitive MRD marker. Using bone marrow (BM) and peripheral blood (PB) samples from 111 patients, we developed a highly sensitive quantitative real-time PCR (qPCR) and digital PCR (dPCR) system capable of detecting fusion mRNAs with a sensitivity of up to 1:100,000. PB samples exhibited sensitivity three orders of magnitude lower compared to BM samples. Patients with an MB4-2 breakpoint demonstrated significantly reduced overall survival (p= 0.003). Our novel method offers a simple and sensitive means for detecting MRD in a substantial proportion of MM patients. Monitoring may be carried out even from PB samples. The literature lacks consensus regarding survival outcomes among patients with differentNSD2breakpoints. Our data align with previous findings indicating that patients with the MB4-2 breakpoint type tend to exhibit unfavorable overall survival.
多发性骨髓瘤是第二常见的血液系统恶性肿瘤。约15%的患者受t(4;14)易位影响，产生IGH::NSD2融合转录本。断裂发生在NSD2基因的三个主要断点区域（MB4-1、MB4-2和MB4-3），其中MB4-1产生全长蛋白，而另两种断裂类型则表达截短蛋白。可测量残留病已被确认为多发性骨髓瘤的关键预后因素。IGH::NSD2融合转录本可作为敏感的MRD标志物。基于111例患者的骨髓与外周血样本，我们建立了高灵敏度的实时定量PCR与数字PCR检测体系，融合mRNA检测灵敏度可达1:100,000。外周血样本的检测灵敏度较骨髓样本低三个数量级。MB4-2断点患者的总体生存期显著缩短（p=0.003）。本检测方法为大部分多发性骨髓瘤患者提供了简便灵敏的MRD监测手段，甚至可通过外周血样本进行监测。目前文献对不同NSD2断点患者的生存结局尚未形成共识，本研究数据与既往发现一致，提示MB4-2断点类型患者往往表现出较差的总体生存预后。
IGH::NSD2Fusion Gene Transcript as Measurable Residual Disease Marker in Multiple Myeloma
肿瘤(癌症)患者之家