A global study for acute myeloid leukemia with RARG rearrangement.
A global study for acute myeloid leukemia with RARG rearrangement.
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DOI：
10.1182/bloodadvances.2022008364
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发表时间：
2023-07-11
期刊：
影响因子：
7.5
通讯作者：
Chen, Su-Ning
中科院分区：
文献类型：
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作者：
Zhu, Hong-Hu;Qin, Ya-Zhen;Zhang, Zhang-Lin;Liu, Yong-Jing;Wen, Li-Jun;You, M. James;Zhang, Cheng;Such, Esperanza;Luo, Hong;Yuan, Hong-Jian;Zhou, Hong-Sheng;Liu, Hong-Xing;Xu, Reng;Li, Ji;Li, Jian-Hu;Hao, Jian-Ping;Jin, Jie;Yu, Liang;Zhang, Jing-Ying;Liu, Li-Ping;Zhang, Le-Ping;Huang, Rui-Bin;Shen, Shu-Hong;Gao, Su-Jun;Wang, Wei;Yan, Xiao-Jing;Zhang, Xin-You;Du, Xin;Chu, Xiao-Xia;Yu, Yan-Fang;Wang, Yi;Mi, Ying-Chang;Lu, Ying;Cai, Zhen;Su, Zhan;Taussig, David Christopher;MacMahon, Suzanne;Ball, Edward D.;Wang, Huan-You;Welch, John S.;Yin, C. Cameron;Borthakur, Gautam;Sanz, Miguel A.;Kantarjian, Hagop M.;Huang, Jin-Yan;Hu, Jiong;Chen, Su-Ning
AML伴RARG重排是一种新的AML亚型，具有一些独特的临床、免疫表型和遗传学特征。RARG重排的AML对ATRA和ATO不敏感，预后差。伴有维甲酸受体γ（RARG）重排的急性髓系白血病（AML）具有与经典急性早幼粒细胞白血病相似的临床、形态学和免疫表型特征。然而，RARG重排的AML对全反式维甲酸（ATRA）和三氧化二砷（ATO）不敏感，预后不良。我们启动了一项全球合作研究，以确定从全球29个研究组/机构收集的RARG重排AML的临床病理学特征、基因组和转录组学特征以及结局。确定了34例RARG重排AML患者。18例（54.5%）患者出现出血或瘀斑。形态学诊断为M3和M3 v的病例分别占73.5%和26.5%。免疫表型：CD 33、CD 13、MPO阳性，CD 38、CD 11b、CD 34、HLA-DR阴性，细胞遗传学检查核型正常者占38%，t（11;12）占26%。RARG的伴侣基因是多样的，包括CPSF 6、NUP 98、HNRNPc、HNRNPm、PML和NPM 1。WT 1-和NRAS/KRAS-突变是常见的突变。34例患者对ATRA和/或ATO均无反应。10例患者（约29%）在诊断后45天内死亡。末次随访时，23例患者死亡，估计2年累积复发率、无事件生存率和总生存率分别为68.7%、26.7%和33.5%。使用来自201名AML患者的RNA测序数据进行的无监督分层聚类显示，81.8%的RARG融合样本聚集在一起，表明一种新的分子亚型。RARG重排是一种新的AML实体，其预后不良。本研究已在中国临床试验注册中心（ChiCTR 2200055810）注册。
AML with RARG rearrangement is a novel subtype of AML with some unique clinical, immunophenotypic, and genetic characteristics. AML with RARG rearrangement is insensitive to ATRA and ATO and carries a poor prognosis. Acute myeloid leukemia (AML) with retinoic acid receptor γ (RARG) rearrangement has clinical, morphologic, and immunophenotypic features similar to classic acute promyelocytic leukemia. However, AML with RARG rearrangement is insensitive to alltrans retinoic acid (ATRA) and arsenic trioxide (ATO) and carries a poor prognosis. We initiated a global cooperative study to define the clinicopathological features, genomic and transcriptomic landscape, and outcomes of AML with RARG rearrangements collected from 29 study groups/institutions worldwide. Thirty-four patients with AML with RARG rearrangements were identified. Bleeding or ecchymosis was present in 18 (54.5%) patients. Morphology diagnosed as M3 and M3v accounted for 73.5% and 26.5% of the cases, respectively. Immunophenotyping showed the following characteristics: positive for CD33, CD13, and MPO but negative for CD38, CD11b, CD34, and HLA-DR. Cytogenetics showed normal karyotype in 38% and t(11;12) in 26% of patients. The partner genes of RARG were diverse and included CPSF6, NUP98, HNRNPc, HNRNPm, PML, and NPM1. WT1- and NRAS/KRAS-mutations were common comutations. None of the 34 patients responded to ATRA and/or ATO. Death within 45 days from diagnosis occurred in 10 patients (∼29%). At the last follow-up, 23 patients had died, and the estimated 2-year cumulative incidence of relapse, event-free survival, and overall survival were 68.7%, 26.7%, and 33.5%, respectively. Unsupervised hierarchical clustering using RNA sequencing data from 201 patients with AML showed that 81.8% of the RARG fusion samples clustered together, suggesting a new molecular subtype. RARG rearrangement is a novel entity of AML that confers a poor prognosis. This study is registered with the Chinese Clinical Trial Registry (ChiCTR2200055810).
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影响因子：
14.9
作者：
Gene Ontology Consortium
通讯作者：
Gene Ontology Consortium
影响因子：
14.9
作者：
Kanehisa M;Furumichi M;Sato Y;Ishiguro-Watanabe M;Tanabe M
通讯作者：
Tanabe M
影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
CPSF6-RARG 融合的急性髓系白血病类似于伴有髓外浸润的急性早幼粒细胞白血病。
影响因子：
3.4
作者：
Han X;Jin C;Zheng G;Li Y;Wang Y;Zhang E;Zhu H;Cai Z
通讯作者：
Cai Z
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W