Department of Pediatrics, Lalla Seràgnoli, Hematology-Oncology Unit, University of Bologna, Italy.
Blood. 2013 Apr 25;121(17):3469-72. doi: 10.1182/blood-2012-11-469825. Epub 2013 Feb 13.
Pediatric cytogenetically normal acute myeloid leukemia (CN-AML) is a heterogeneous subgroup of myeloid clonal disorders that do not harbor known mutations. To investigate the mutation spectrum of pediatric CN-AML, we performed whole-transcriptome massively parallel sequencing on blasts from 7 CN-AML pediatric patients. In 3 patients we identified a recurrent cryptic inversion of chromosome 16, encoding a CBFA2T3-GLIS2 fusion transcript. In a validation cohort of 230 pediatric CN-AML samples we identified 17 new cases. Among a total of 20 patients with CBFA2T3-GLIS2 fusion transcript out of 237 investigated (8.4%), 10 patients (50%) did not belong to the French-American-British (FAB) M7 subgroup. The 5-year event-free survival for these 20 children was worse than that for the other CN-AML patients (27.4% vs 59.6%; P = .01). These data suggest that the presence of CBFA2T3-GLIS2 fusion transcript is a novel common feature of pediatric CN-AML, not restricted to the FAB M7 subtype, predicting poorer outcome.
儿科细胞遗传学正常急性髓系白血病（CN-AML）是一组异质性的髓系克隆性疾病亚群，不携带已知的突变。为了研究儿科 CN-AML 的突变谱，我们对 7 例 CN-AML 儿科患者的原始细胞进行了全转录组大规模平行测序。在 3 例患者中，我们发现了 16 号染色体的一种反复出现的隐匿性倒位，编码 CBFA2T3-GLIS2 融合转录本。在 230 例儿科 CN-AML 样本的验证队列中，我们鉴定出了 17 例新病例。在总共 237 例被研究的患者中，有 20 例存在 CBFA2T3-GLIS2 融合转录本（8.4%），其中 10 例（50%）不属于法美英（FAB）M7 亚型。这 20 名儿童的 5 年无事件生存情况比其他 CN-AML 患者差（27.4% vs 59.6%；P =.01）。这些数据表明，CBFA2T3-GLIS2 融合转录本的存在是儿科 CN-AML 的一种新的共同特征，不仅限于 FAB M7 亚型，预示着更差的预后。
