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RAG1和RAG2非核心区域涉及白血病发生和非标V(D) J重组在BCR-ABL1驱动的B细胞系的淋巴细胞白血病中

Xiaozhuo Yu¹, Wen Zhou¹, Xiaodong Chen¹

¹Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.

|July 26, 2024

概括

非核心RAG区域,特别是RAG1,对于精确的V(D) J重组和BCR-ABL1+B-ALL.中的基因组稳定性至关重要. 它们的缺失增加了白血病细胞的恶性特征和非向突变.

科学领域:

遗传学遗传学是一个
分子生物学分子生物学
癌症研究癌症研究

背景情况:

RAG复合体调解V(D) J重组,这对于适应性免疫是必不可少的.
目标外V(D) J重组与淋巴发育有关,RAG2的C端缺失在某些小鼠模型中使其恶化.
RAG1和RAG2非核心区域在抑制非目标重组和维护BCR-ABL1+B-ALL基因组稳定的作用尚不清楚.

研究的目的:

研究RAG非核心区域对基因组稳定性和BCR-ABL1+B-ALL中的V(D) J重组精度的影响.
描述RAG非核心区域抑制非目标V(D) J重组的机制.

主要方法:

为BCR-ABL1+ B-ALL建立了三种小鼠模型:全长RAG (Rag^f/f),核心RAG1 (Rag1^c/c) 和核心RAG2 (Rag2^c/c).
在模型中对白血病细胞特征,非目标V(D) J重组频率,瘤突变和RAG裂变精度进行比较分析.

主要成果:

缺乏非核心RAG区域 (Rag^c/c和Rag2^c/c) 的白血病细胞表现出更具侵略性的瘤特征.
与具有全长RAG的细胞相比,这些细胞还显示出非目标V(D) J重组和瘤突变的频率更高.
在Rag1^c/c细胞中观察到RAG裂变精度降低和更小的重组大小,可能会增加目标外事件.

结论:

非核心RAG区域,特别是RAG1的RAG区域,对于保持V(D) J重组的精度至关重要.
在BCR-ABL1+ B-ALL.的背景下,这些区域在保持基因组稳定性方面发挥着重要作用.
非核心RAG区域的损失通过增加非目标重组和突变,有助于淋巴发育.

关键词:

BCR-ABL1+ B细胞急性淋巴细胞白血病在 RAG 蛋白质中.V(D) J的重组组合.免疫学免疫学免疫学这是一种炎症炎症炎症炎症.这里是鼠标鼠标鼠标鼠标鼠标鼠标.

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