Translocation t(4;12)(q11-13;p13) is a recurrent but very rare chromosomal aberration in acute myeloid leukaemia (AML) resulting in the non-constant expression of a CHIC2/ETV6 fusion transcript. We report clinico-biological features, molecular characteristics and outcomes of 21 cases of t(4;12) including 19 AML and two myelodysplastic syndromes (MDS). Median age at the time of t(4;12) was 78 years (range, 56–88). Multilineage dysplasia was described in 10 of 19 (53%) AML cases and CD7 and/or CD56 expression in 90%. FISH analyses identified ETV6 and CHIC2 region rearrangements in respectively 18 of 18 and 15 of 17 studied cases. The t(4;12) was the sole cytogenetic abnormality in 48% of cases. The most frequent associated mutated genes were ASXL1 (n = 8/16, 50%), IDH1/2 (n = 7/16, 44%), SRSF2 (n = 5/16, 31%) and RUNX1 (n = 4/16, 25%). Interestingly, concurrent FISH and molecular analyses showed that t(4;12) can be, but not always, a founding oncogenic event. Median OS was 7.8 months for the entire cohort. In the 16 of 21 patients (76%) who received antitumoral treatment, overall response and first complete remission rates were 37% and 31%, respectively. Median progression-free survival in responders was 13.7 months. Finally, t(4;12) cases harboured many characteristics of AML with myelodysplasia-related changes (multilineage dysplasia, MDS-related cytogenetic abnormalities, frequent ASXL1 mutations) and a poor prognosis.

中文翻译：

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易位 t(4;12)(q11-13;p13) 的髓系恶性肿瘤：分子景观、克隆等级和临床结果

易位 t(4;12)(q11-13;p13) 是急性髓性白血病 (AML) 中反复出现但非常罕见的染色体畸变，导致CHIC2 / ETV6融合转录本的非恒定表达。我们报告了 21 例 t(4;12) 病例的临床生物学特征、分子特征和结果，包括 19 例 AML 和 2 例骨髓增生异常综合征 (MDS)。t(4;12) 时的中位年龄为 78 岁（范围，56-88）。在 19 例 (53%) AML 病例中有 10 例（53%）描述了多系发育异常，并且 90% 有 CD7 和/或 CD56 表达。FISH 分析确定了ETV6和CHIC218 个研究案例中的 18 个和 17 个研究案例中的 15 个区域重新排列。在 48% 的病例中，t(4;12) 是唯一的细胞遗传学异常。最常见的相关突变基因是ASXL1 (n = 8/16, 50%)、IDH1 / 2 (n = 7/16, 44%)、SRSF2 (n = 5/16, 31%) 和RUNX1(n = 4/16, 25%)。有趣的是，同时进行的 FISH 和分子分析表明 t(4;12) 可能是，但并不总是，一个创始致癌事件。整个队列的中位 OS 为 7.8 个月。在接受抗肿瘤治疗的 21 名患者中的 16 名（76%）中，总体缓解率和首次完全缓解率分别为 37% 和 31%。应答者的中位无进展生存期为 13.7 个月。最后，t(4;12) 病例具有 AML 的许多特征，伴有骨髓增生异常相关的变化（多系发育不良、MDS 相关的细胞遗传学异常、频繁的ASXL1 突变）和预后不良。