Identification of a novel CPSF6-RARG fusion transcript in acute myeloid leukemia resembling acute promyelocytic leukemia
Identification of a novel CPSF6-RARG fusion transcript in acute myeloid leukemia resembling acute promyelocytic leukemia
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鉴定类似急性早幼粒细胞白血病的急性髓细胞白血病中的新型 CPSF6-RARG 融合转录本
DOI：
10.1038/s41375-018-0095-z
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发表时间：
2018-10-01
期刊：
影响因子：
11.4
通讯作者：
Zhu, Hong-Hu
中科院分区：
文献类型：
--
作者：
Qin, Ya-Zhen;Huang, Xiao-Jun;Zhu, Hong-Hu
裂解和多聚腺苷酸化特异性因子6（CPSF 6）是裂解因子I的大亚基，其是最初被鉴定为替代裂解和多聚腺苷酸化过程中的中心参与者的RNA结合蛋白复合物。1 CPSF 6和Nudt 21复合物结合RNA并促进RNA成环，允许替代mRNA 3′端加工。2 CPSF 6单独控制指定HIV-1整合前复合物运输到活性染色质的关键分子相互作用。最近，CPSF 6被发现在乳腺癌侵袭性中起着至关重要的作用。4然而，CPSF 6在白血病中的作用至今未见报道。在这里，我们报告了第一例新的CPSF 6-维甲酸受体γ（RARG）（CPSF 6-RARG）融合转录，显示经典的高颗粒急性早幼粒细胞白血病（APL）的形态学和免疫表型特征。一名38岁男性因口腔出血和皮肤瘀斑入院。他的血细胞计数显示白色血细胞计数为1.68× 109/L，包括10%的早幼粒细胞;血红蛋白水平为80 g/L;血小板计数为79× 109/L。他的凝血酶原时间、纤维蛋白原、纤维蛋白降解产物和D-二聚体水平分别为14.2 s（参考9.4-12.5 s）、115 mg/dl（参考200-400）、2359 µg/ml（参考0-5）和32，513 ng/ml（参考0-243）。他的活化部分凝血活酶时间在正常范围内。骨髓（BM）涂片显示细胞过多，65%的颗粒早幼粒细胞过多（图1a）。骨髓组织化学显示APL的典型模式（图1b）。白血病细胞表达髓过氧化物酶、CD 117、CD 123、CD 34、CD 33和CD 13，部分表达CD 9和CD 64，但缺乏CD 11b、HLA-DR、CD 38、CD 56、CD 14和其他T淋巴或B淋巴相关标志物的表达。该患者的推定诊断为APL。然而，逆转录-聚合酶链反应和荧光原位杂交均未能检测到PML。
Cleavage and polyadenylation specific factor 6 (CPSF6) is a large subunit of cleavage factor I, which is an RNA-binding protein complex that was originally identified as a central player in the alternative cleavage and polyadenylation process. 1 The CPSF6 and Nudt21 complex binds RNA and facilitates RNA looping, allowing alternative mRNA 3′ end processing. 2 CPSF6 alone controls the key molecular interactions that specify HIV-1 pre-integration complex trafficking to active chromatin. 3 Recently, CPSF6 was found to play a vital role in breast cancer aggressiveness. 4 However, the role of CPSF6 in leukemia has not been reported so far. Here, we report the first case with a novel CPSF6-retinoic acid receptor gamma (RARG)(CPSF6-RARG) fusion transcript, showing morphological and immunophenotypical features of classical hypergranular acute promyelocytic leukemia (APL). A 38-year-old man was admitted due to oral hemorrhage and skin ecchymosis. His blood count showed a white blood cell count of 1.68× 109/L, including 10% promyelocytes; a hemoglobin level of 80 g/L; and a platelet count of 79× 109/L. His prothrombin time, fibrinogen, fibrin degradation products, and D-dimer levels were 14.2 s (ref. 9.4–12.5 s), 115 mg/dl (ref. 200–400, 2359 µg/ml (ref. 0–5), and 32,513 ng/ml (ref. 0–243), respectively. His activated partial thromboplastin time was within the normal range. A bone marrow (BM) smear showed hypercellularity, with 65% hypergranular promyelocytes (Fig. 1a). The BM histochemistry showed the typical pattern of APL (Fig. 1b). The leukemia cells expressed myeloperoxidase, CD117, CD123, CD34, CD33 and CD13 and partially expressed CD9 and CD64, but lacked the expression of CD11b, HLA-DR, CD38, CD56, CD14 and other T-lymphoid-related or B-lymphoid-related markers. The presumptive diagnosis of this patient was APL. However, both the reverse transcription-polymerase chain reaction and fluorescence in situ hybridization failed to detect the PML-