High EVI1 Expression due to NRIP1/EVI1 Fusion in Therapy-related Acute Myeloid Leukemia: Description of the First Pediatric Case.
High EVI1 Expression due to NRIP1/EVI1 Fusion in Therapy-related Acute Myeloid Leukemia: Description of the First Pediatric Case.
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DOI：
10.1097/hs9.0000000000000471
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发表时间：
2020-10
期刊：
影响因子：
6.6
通讯作者：
Cazzaniga G
中科院分区：
文献类型：
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作者：
D'Angiò M;Fazio G;Grioni A;Palamini S;Sala S;Galbiati M;Biondi A;Balduzzi A;Rizzari C;Cazzaniga G
在急性髓性白血病（AML）、慢性髓性白血病（CML）和骨髓增生异常综合征（MDS）中，3号染色体3q 26带的破坏已被充分记录。1临床上，3q 26。2重排与血小板计数升高、巨核细胞明显增生伴异型增生、侵袭性临床病程和常规治疗预后不良相关。2，3染色体3q 26异常已被报道激活人亲嗜性病毒整合位点-1基因（EVI 1，称为MECOM-MDS 1和EVI 1复合基因座）的异常表达，所述基因是在造血干细胞的增殖和维持中具有重要作用的转录因子。4，5尽管EVI 1在白血病发生中的确切作用尚不完全清楚，但最近的一项研究表明，它可能通过调节miR-9启动子甲基化参与白血病细胞增殖和凋亡，从而表明低甲基化剂在EVI 1过度表达的白血病中可能发挥作用。6-8 EVI 1上调发生在约8%至10%的成人AML中，并且惊人地，高达27%的儿科KMT 2A（MLL）重排白血病病例中。导致EVI 1不适当激活的最常见异常是倒位inv（3）（q21; q26）和易位t（3; 3）（q21; q26）。2）。然而，EVI 1可以与多种其他伴侣基因重排[1 q41（DUSP 10），7 q21（CDK 6），7 q34（TCRB），12 p34（ETV 6），21 q22（RUNX 1）]。3，11-12在细胞遗传学正常的AML中，在异常的细胞遗传学亚组中，如单体7和11 q23/MLL易位，以及在具有隐性3q 26重排的患者中也可以检测到其增加的表达。特别是，迄今为止，使用FISH分析在9名成人、4名AML和5名MDS中鉴定了导致NRIP 1/EVI 1融合的隐藏t（3; 21）（q26; q11）重排。12所有患者均显示高EVI 1表达和不良预后，中位总生存期（OS）为9.4个月。
Disruption of chromosome 3 at band 3q26 has been well-documented in acute myeloid leukemia (AML), chronic myeloid leukemia (CML) and myelodysplastic syndromes (MDS). 1 Clinically, 3q26. 2 rearrangements correlate with elevated platelet counts, marked hyperplasia with dysplasia of megakaryocytes, aggressive clinical course and unfavorable prognosis with conventional therapy. 2, 3 Chromosome 3q26 abnormalities have been reported to activate the aberrant expression of the human Ecotropic Virus Integration site-1 gene (EVI1 known as MECOM-MDS1 and EVI1 complex locus), a transcriptional factor with an essential role in proliferation and maintenance of hematopoietic stem cells. 4, 5 Although the exact role of EVI1 in leukemogenesis is not completely known, a recent study revealed that it may be involved in leukemic cell proliferation and apoptosis via the regulation of miR-9 promoter methylation, thus suggesting the possible role of hypomethylating agents in EVI1 over-expressed leukaemia. 6–8 EVI1 up regulation occurs in approximately 8% to 10% of human adult AML and, strikingly, up to 27% of pediatric KMT2A (MLL) rearranged leukemia cases. 9, 10 The most frequent abnormalities resulting in inappropriate activation of EVI1 are the inversion inv (3)(q21q26) and the translocation t (3; 3)(q21; q26. 2). However, EVI1 can be rearranged with a variety of other partner genes [1q41 (DUSP10), 7q21 (CDK6), 7q34 (TCRB), 12p34 (ETV6), 21q22 (RUNX1)]. 3, 11–12 Its increased expression can also be detected in cytogenetically normal AML, in aberrant cytogenetic subgroups, such as monosomy 7 and 11q23/MLL translocations, as well as in patients with cryptic 3q26 rearrangements. 3, 12 In particular, the cryptic t (3; 21)(q26; q11) rearrangement, resulting in NRIP1/EVI1 fusion, has been identified using FISH analyses in 9 adults, 4 AML and 5 MDS so far. 12 All patients showed a high EVI1 expression and an adverse prognosis with a median overall survival (OS) of 9.4 months.