The molecular ontogeny of follicular lymphoma: gene mutations succeeding the BCL2 translocation define common precursor cells.
The molecular ontogeny of follicular lymphoma: gene mutations succeeding the BCL2 translocation define common precursor cells.
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滤泡性淋巴瘤的分子个体发育：BCL2 易位后的基因突变定义了常见的前体细胞。
DOI：
10.1111/bjh.17990
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发表时间：
2022
影响因子：
6.5
通讯作者：
Ruland,
中科院分区：
文献类型：
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作者：
Haebe,Sarah;Keay,William;Alig,Stefan;Mohr,Anne-Wiebe;Martin,LarissaK;Heide,Michael;Secci,Ramona;Krebs,Stefan;Blum,Helmut;Moosmann,Andreas;LouissaintJr,Abner;Weinstock,DavidM;Thoene,Silvia;vonBergwelt-Baildon,Michael;Ruland,
复发性滤泡性淋巴瘤（FL）可由共同祖细胞（CPC）引起。从概念上讲，CPC定义突变是初始和复发肿瘤共有的体细胞改变，主要是B细胞白血病/淋巴瘤2（BCL 2）/免疫球蛋白重基因座（IGH）易位和其他复发性基因突变。通过高灵敏度突变检测的互补方法，我们没有在3例复发性FL患者的临床缓解样本中发现高度纯化的BCL 2/IGH阴性造血祖细胞中的CPC定义突变。相反，我们发现细胞携带相同的BCL 2/IGH易位，但缺乏CREB结合蛋白（CREBBP），赖氨酸甲基转移酶2D（KMT 2D）和其他复发性基因突变。因此，（i）BCL 2/IGH易位可以先于人类FL中CPC定义的突变，并且（ii）BCL 2/IGH易位的细胞可以持续临床缓解。
Relapsed follicular lymphoma (FL) can arise from common progenitor cells (CPCs). Conceptually, CPC‐defining mutations are somatic alterations shared by the initial and relapsed tumours, mostly B‐cell leukaemia/lymphoma 2 (BCL2)/immunoglobulin heavy locus (IGH) translocations and other recurrent gene mutations. Through complementary approaches for highly sensitive mutation detection, we do not find CPC‐defining mutations in highly purifiedBCL2/IGH‐negative haematopoietic progenitor cells in clinical remission samples from three patients with relapsed FL. Instead, we find cells harbouring the sameBCL2/IGHtranslocation but lackingCREBbinding protein (CREBBP), lysine methyltransferase 2D (KMT2D) and other recurrent gene mutations. Thus, (i) theBCL2/IGHtranslocation can precede CPC‐defining mutations in human FL, and (ii)BCL2/IGH‐translocated cells can persist in clinical remission.