Immunoglobulin gene rearrangement IGHV3-48 is a predictive marker of histological transformation into aggressive lymphoma in follicular lymphomas
Immunoglobulin gene rearrangement IGHV3-48 is a predictive marker of histological transformation into aggressive lymphoma in follicular lymphomas
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DOI：
10.1038/s41408-019-0213-9
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发表时间：
2019-06-17
影响因子：
12.8
通讯作者：
Alcoceba, Miguel
中科院分区：
文献类型：
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作者：
Garcia-Alvarez, Maria;Alonso-Alvarez, Sara;Alcoceba, Miguel
滤泡性淋巴瘤（FL）是一种异质性疾病，其发病机制仍部分不明。大约20%的FL患者经历早期进展或治疗难治性疾病，并且每年2-3%的患者经历组织学转化（HT）为更具侵袭性的淋巴瘤（tFL）。在这里，我们评估免疫球蛋白重链可变区（IGHV）基因的使用和突变状态在187例FL的情况下，以评估其对临床结果和组织学转化的影响。IGHV基因库在FL中有明显的偏向性，IGHV 4 -34（14%）、IGHV 3 -23（14%）、IGHV 3 -48（10%）、IGHV 3 -30（9%）和IGHV 3 -21（7%）基因占整个队列的一半以上。与5年时未转化FL（5%，P=0.05）相比，IGHV 3 -48在tFL病例中的代表性过高（19%）。携带IGHV 3 -48基因的患者在10年后患HT的可能性显著高于使用其他基因的患者（71% vs. 25%，P < 0.05），无论他们接受了何种治疗。此外，IGHV 3 -30在FL（9%）和tFL（13%）病例中也过度表达，而弥漫性大B细胞淋巴瘤中几乎不存在IGHV 3 - 30。总之，我们的结果表明抗原选择在FL的发展中的作用，而IGHV 3 -48的使用可以帮助预测组织学转化。
Follicular lymphoma (FL) is a heterogeneous disease whose pathogenesis remains partially unknown. Around 20% of FL patients experience early progression or treatment-refractory disease and 2-3% of patients per year experience histological transformation (HT) into a more aggressive lymphoma (tFL). Here, we evaluate the immunoglobulin heavy chain variable (IGHV) gene usage and mutational status in 187 FL cases to assess its impact on clinical outcome and histological transformation. The IGHV gene repertoire was remarkably biased in FL. The IGHV4-34 (14%), IGHV3-23 (14%), IGHV3-48 (10%), IGHV3-30 (9%) and IGHV3-21 (7%) genes accounted for more than half of the whole cohort. IGHV3-48 was overrepresented in cases of tFL (19%) compared with non-transformed FL at 5 years (5%, P=0.05). Patients with the IGHV3-48 gene were significantly more likely to have had HT after 10 years than those who used other genes (71% vs. 25%, P < 0.05), irrespective of the therapy they received. Moreover, IGHV3-30 was also overrepresented in cases of FL (9%) and tFL (13%) compared with diffuse large B-cell lymphoma in which it was nearly absent. In conclusion, our results indicate a role for antigen selection in the development of FL, while the use of IGHV3-48 could help predict histological transformation.