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.

中文翻译：

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下一代测序揭示了急性髓性白血病中具有特定突变热点的独特免疫球蛋白库

免疫球蛋白 (Ig) 被称为 B 淋巴细胞发挥抗体功能的标志。然而，我们之前的研究表明，来自急性髓性白血病 (AML) 患者的成髓细胞也可以表达具有不同作用的 Ig。在这里，我们通过实时 PCR 对 Ig（IGHG 和 IGK）转录物进行了量化，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 原始细胞表达。更高水平的 AML 衍生的 IGHG 表达与显着更短的无病生存期相关。下一代测序揭示了 AML 中所有五种 Ig 类别（IGHA、IGHD、IGHE、IGHG 和 IGHM）和两种 Ig 类型（IGK 和 IGL）的失调转录本。成髓细胞中的 VH-D-JH 重排偏向于个体特异性，而不是像 B 细胞中那样普遍多样化。与 AML 衍生的 IgH 相比，AML 衍生的 IGK 在不同的 AML 样本中更为保守。经常共享的 Vκ-Jκ 模式是 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 细胞中的经典 IGK 的不同之处在于丝氨酸密码子的高突变率和特殊的突变热点。成髓细胞中不同 Ig 库的发现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。