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Blood:DUSP22重组型间变性大细胞淋巴瘤!

2018-08-13 MedSci MedSci原创

中心点:DUSP22重组型间变性大细胞淋巴瘤(ALCLs)属于缺乏活化STAT3的ALCLs的一种独特的亚型。DUSP22重组型ALCLs具有独特的DNA低甲基化和免疫原性表型的分子特征。摘要:间变性大细胞淋巴瘤(ALCLs)是CD33阳性的T细胞非霍奇金淋巴瘤,广泛分为ALK阳性和ALK阴性两种类型。ALK阳性ALCLs持续存在ALK酪氨酸激酶基因重组,而ALK阴性ALCLs具有临床和遗传异质性

中心点:

DUSP22重组型间变性大细胞淋巴瘤(ALCLs)属于缺乏活化STAT3的ALCLs的一种独特的亚型。

DUSP22重组型ALCLs具有独特的DNA低甲基化和免疫原性表型的分子特征。

摘要:

间变性大细胞淋巴瘤(ALCLs)是CD33阳性的T细胞非霍奇金淋巴瘤,广泛分为ALK阳性和ALK阴性两种类型。ALK阳性ALCLs持续存在ALK酪氨酸激酶基因重组,而ALK阴性ALCLs具有临床和遗传异质性。约30%的ALK阴性ALCLs具有DUSP22重组,标准疗法可获得良好的长期预后。为了更好的了解这组肿瘤,Rebecca A. Luchtel等人采用基因表达谱分析其分子特征。

DUSP22重组的ALCLs属于缺乏与JAK-STAT3信号(该通路在大部分ALCLs中对肿瘤生长至关重要)相关基因表达的ALCLs的一种独特的亚型。反相蛋白试验和免疫组化研究发现在DUSP22重组型ALCLs中缺少激活的STAT3。DUSP22重组型ALCLs还过表达免疫原性癌睾丸抗原(CTA)基因,并表现出显著的DNA低甲基化。

通过药物将ALCL细胞DNA去甲基化可再现CTAs和其他DUSP22信号基因过表达。此外,与其他型ALCLs相比,DUSP22重组型ALCLs PD-L1的表达水平最低,但共刺激基因CD58和II型HLA高表达。

总而言之,本研究表明DUSP22重组将ALCLs划分出一种具有独特分子特征的亚型,与抗原性、共刺激分子表达和PD-1/PD-L1免疫检查点失活相关的免疫原性提示可能促进该类疾病患者预后良好。或许我们可通过去甲基化制剂和(或)免疫检查点抑制剂将更为侵袭性的ALCLs重组成DUSP22样的免疫原性分子,以提高其患者预后。

原始出处:

Rebecca A. Luchtel, et al. Molecular profiling reveals immunogenic cues in anaplastic large cell lymphomas with DUSP22 rearrangements. Blood  2018  :blood-2018-03-838524;  doi: https://doi.org/10.1182/blood-2018-03-838524

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    2018-08-16 zhaohui6731
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    2018-08-15 huangdf
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