Abstract：
Immunoglobulin (Ig) is known as a hallmark of B-lymphocytes exerting antibody functions. However, our previous studies demonstrated that myeloblasts from acute myeloid leukemia (AML) patients could also express Ig with distinct roles. Here, we quantified Ig (IGHG and IGK) transcripts by real-time PCR and performed a comprehensive analysis of Ig repertoire (both heavy chains and light chains) in AML blasts. We found that Ig was frequently expressed by AML blasts. A higher level of AML-derived IGHG expression correlated with a significantly shorter disease-free survival. Next-generation sequencing revealed dysregulated transcripts of all five Ig classes (IGHA, IGHD, IGHE, IGHG, and IGHM) and two Ig types (IGK and IGL) in AML. VH-D-JH rearrangements in myeloblasts were biased with individual specificity rather than generally diverse as in B-cells. Compared to AML-derived IgH, AML-derived IGK was more conserved among different AML samples. The frequently shared Vκ-Jκ patterns were IGKV3-20*01/IGKJ1*01, IGKV2D-28*01/IGKJ1*01, and IGKV4-1*01/IGKJ1*01. Moreover, AML-derived IGK was different from classical IGK in B-cells for the high mutation rates and special mutation hotspots at serine codons. Findings of the distinct Ig repertoire in myeloblasts may facilitate the discovery of a new molecular marker for disease monitoring and target therapy.
摘要：
已知免疫球蛋白(Ig)是发挥抗体功能的B淋巴细胞的标志。然而,我们之前的研究表明,急性髓细胞性白血病(AML)患者的成髓细胞也可以表达具有不同作用的Ig.这里,我们通过实时PCR定量Ig(IGHG和IGK)转录本,并对AML母细胞中的Ig库(重链和轻链)进行了全面分析.我们发现Ig经常由AML母细胞表达。较高水平的AML衍生的IGHG表达与显著较短的无病生存期相关。下一代测序揭示了所有五个Ig类的转录物失调(IGHA，IGHD,IGHE,IGHG,和IGHM）和AML中的两种Ig类型（IGK和IGL）。成髓细胞中的VH-D-JH重排偏向于个体特异性，而不是像B细胞中那样通常不同。与AML衍生的IgH相比，AML来源的IGK在不同AML样本中更为保守。常见的Vκ-Jκ模式为IGKV3-20*01/IGKJ1*01、IGKV2D-28*01/IGKJ1*01和IGKV4-1*01/IGKJ1*01。此外，AML衍生的IGK与B细胞中经典IGK的不同之处在于丝氨酸密码子的高突变率和特殊突变热点。发现成髓细胞中不同的Ig库可能有助于发现用于疾病监测和靶向治疗的新分子标志物。
