Immunoglobulin gamma heavy chain gene with somatic hypermutation is frequently expressed in acute myeloid leukemia
Immunoglobulin gamma heavy chain gene with somatic hypermutation is frequently expressed in acute myeloid leukemia
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DOI：
10.1038/leu.2012.184
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发表时间：
2013-01-01
期刊：
影响因子：
11.4
通讯作者：
Yin, C. C.
中科院分区：
文献类型：
--
作者：
Qiu, X.;Sun, X.;Yin, C. C.
免疫球蛋白（IG）是B细胞的特征性标志物，已报道其在上皮细胞中的表达，并已表明其在上皮细胞的存活和生长中起作用。我们评估了IG γ重链（IgG）在急性髓性白血病（AML）中表达的频率和水平，发现IgG在AML细胞系和原代成髓细胞中以高频率和水平表达，但在非造血系统肿瘤患者或健康对照的单核细胞或中性粒细胞中不表达。AML衍生的IgG与B细胞衍生的IgG具有相同的分子量，并且是分泌的。我们进一步检测了AML细胞系中的IgG V（H）DJ（H）转录物，并分选了原代成髓细胞，证实IgG表达确实由AML细胞产生。AML衍生的IgG基因重排显示了可变（V）基因片段的体细胞超突变的证据，以及限制性（AML细胞系）或偏向性（原代成髓细胞）V使用。抗人IgG在AML细胞系中降低细胞活力并诱导细胞凋亡。虽然AML衍生IgG的功能尚不清楚，但我们的研究结果表明，AML衍生IgG可能是一种新的AML相关基因，有助于白血病发生和AML进展。AML源性IgG可作为监测微小残留病或设计靶向治疗的有用分子标志物。白血病（2013）27，92-99; doi：10.1038/leu.2012.184
Expression of immunoglobulin (Ig), a marker characteristic of B cells, has been reported in epithelial cells and has been suggested to have a role in their survival and growth. We assessed the frequency and level of Ig gamma heavy chain (IgG) expression in acute myeloid leukemia (AML), and found that IgG was expressed at a high frequency and level in AML cell lines and primary myeloblasts, but not in monocytes or neutrophils from patients with non-hematopoietic neoplasms or healthy controls. AML-derived IgG had the same molecular weight as B cell-derived IgG and was secreted. We further detected IgG V(H)DJ(H) transcripts in AML cell lines and sorted primary myeloblasts, confirming that IgG expression was indeed produced by AML cells. AML-derived IgG gene rearrangements showed evidence of somatic hypermutation of the variable (V) gene segments, and restricted (AML cell lines) or biased (primary myeloblasts) V usage. Anti-human IgG reduced cell viability and induced apoptosis in AML cell lines. Although the function of the AML-derived IgG is unclear, our findings suggest that AML-derived IgG may be a novel AML-related gene that contributes to leukemogenesis and AML progression. AML-derived IgG may serve as a useful molecular marker for monitoring minimal residual disease or designing target therapy. Leukemia (2013) 27, 92-99; doi:10.1038/leu.2012.184