ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes
ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes
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DOI：
10.1182/blood-2014-04-571091
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发表时间：
2014-08-28
期刊：
影响因子：
20.3
通讯作者：
Feldman, Andrew L.
中科院分区：
文献类型：
--
作者：
Castellar, Edgardo R. Parrilla;Jaffe, Elaine S.;Feldman, Andrew L.
间变性淋巴瘤激酶（ALK）阴性间变性大细胞淋巴瘤（ALCL）是一种CD 30阳性T细胞非霍奇金淋巴瘤，其形态类似于ALK阳性ALCL，但缺乏ALK基因的染色体重排。尚未描述ALK阴性ALCL的遗传和临床异质性。我们对73例ALK阴性ALCL和32例ALK阳性ALCL进行了免疫组织化学和荧光原位杂交，并评估了病理学、遗传学和临床结局之间的相关性。分别在30%和8%的ALK阴性ALCL中发现了DUSP 22和TP 63的染色体重排。这些重排是相互排斥的，在ALK阳性ALCL中不存在。ALK阳性ALCL的5年总生存率为85%，DUSP 22重排ALCL为90%，TP 63重排ALCL为17%，缺乏所有3种遗传标记的病例为42%（P < .0001）。校正国际预后指数和年龄后，这4组的死亡风险比分别为1.0（参考组）、0.58、8.63和4.16（P = 7.10 x 10（-5））。当仅限于接受蒽环类药物化疗的患者以及未接受干细胞移植的患者时，这些结果相似。因此，ALK阴性ALCL是一种遗传异质性疾病，标准治疗后结局差异很大。DUSP 22和TP 63重排可以作为预测性生物标志物，帮助指导患者管理。
Anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL) is a CD30-positive T-cell non-Hodgkin lymphoma that morphologically resembles ALK-positive ALCL but lacks chromosomal rearrangements of the ALK gene. The genetic and clinical heterogeneity of ALK-negative ALCL has not been delineated. We performed immunohistochemistry and fluorescence in situ hybridization on 73 ALK-negative ALCLs and 32 ALK-positive ALCLs and evaluated the associations among pathology, genetics, and clinical outcome. Chromosomal rearrangements of DUSP22 and TP63 were identified in 30% and 8% of ALK-negative ALCLs, respectively. These rearrangements were mutually exclusive and were absent in ALK-positive ALCLs. Five-year overall survival rates were 85% for ALK-positive ALCLs, 90% for DUSP22-rearranged ALCLs, 17% for TP63-rearranged ALCLs, and 42% for cases lacking all 3 genetic markers (P < .0001). Hazard ratios for death in these 4 groups after adjusting for International Prognostic Index and age were 1.0 (reference group), 0.58, 8.63, and 4.16, respectively (P = 7.10 x 10(-5)). These results were similar when restricted to patients receiving anthracycline-based chemotherapy, as well as to patients not receiving stem cell transplantation. Thus, ALK-negative ALCL is a genetically heterogeneous disease with widely disparate outcomes following standard therapy. DUSP22 and TP63 rearrangements may serve as predictive biomarkers to help guide patient management.