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Nat Commun:全基因组关联研究鉴定慢性淋巴细胞白血病的危险基因座

2021-02-05 xiaozeng MedSci原创

慢性淋巴细胞性白血病(CLL)是一种普遍的血液系统恶性肿瘤,英国每年约有3750例新确诊的病例。

慢性淋巴细胞性白血病(CLL)是一种普遍的血液系统恶性肿瘤,英国每年约有3750例新确诊的病例。CLL的特征在于明显的临床和生物学异质性,一部分患者患有稳定的无症状疾病且不需要治疗的干预,而其他的患者则呈现出进行性疾病,并伴随着生存期的缩短。

高效的化学免疫疗法目前是有症状的CLL患者的一个治疗策略,B细胞受体信号通路抑制剂(BCRi)和靶向抗凋亡蛋白的药物的出现以及二者的高效联合治疗方案的出现可能会改善患者的预后。

进展性CLL相关位点的区域关联和连锁不平衡图

患者一级亲属的CLL发生率增加也是该疾病遗传易感性的一个因素,大规模的全基因组关联研究(GWAS)也已证实了这一点。鉴于对CLL易感性的重要遗传贡献,研究人员假设固有遗传突变会影响疾病的发生发展,且对于患者的预后具有重要意义。

进展性CLL相关位点的森林图和生存曲线

研究人员从来自七项涉及842例病例的研究的汇总数据确定了与诊断到治疗时间相关的两个基因组位点,包括10q26.13(rs736456)和6p(rs3778076),其是早期CLL患者的有力的预后指标。基因表达的数量性状基因座分析确定了与调节B细胞受体或先天性免疫反应这一CLL发病的关键途径相关的假定功能基因。


总而言之,该研究结果揭示,rs736456和rs3778076是CLL的预后指标,该结果也表明,疾病的发生发展由固有遗传突变以及已知的体细胞驱动因素所决定。


原始出处:

Lin, WY., Fordham, S.E., Sunter, N. et al. Genome-wide association study identifies risk loci for progressive chronic lymphocytic leukemia. Nat Commun 12, 665 (28 January 2021).

 

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    2022-01-08 liuli5079
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    2021-08-06 liye789132251
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    2021-02-07 jichang
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    2021-02-06 carrotlyl

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