t(7;12)(q36;p13) 易位的急性髓系白血病 (AML) 仅发生在非常年幼的儿童中，并且临床结果较差。仅在一小部分病例中报告了断点伙伴（MNX1 和 ETV6）之间预期的肿瘤融合。然而，一个普遍特征是 MNX1 的强转录和蛋白质表达，MNX1 是一种同源盒转录因子，通常不在造血细胞中表达。在这里，我们将受影响患者的 7 号和 12 号染色体上的易位断点映射到靠近 MNX1 和 ETV6 内含子 1 或 2 的区域。 MNX1 在儿科 AML 中过度表达的频率（n=1556，自己和发表的数据）为 2.4%，主要发生在 t(7;12)(q36;p13) AML 中。 t(7;12)(q36;p13) iPSC 细胞系模型中的染色质相互作用测定揭示了增强子劫持事件，该事件解释了造血细胞中 MNX1 的过度表达。我们的数据表明，增强子劫持可能是未发现肿瘤融合产物的易位的更广泛后果，包括例如t(1;3) 或 t(4;12) AML。版权所有 © 2024 美国血液学会。

Acute myeloid leukemia (AML) with the t(7;12)(q36;p13) translocation occurs only in very young children and has a poor clinical outcome. The expected oncofusion between breakpoint partners (MNX1 and ETV6) has only been reported in a subset of cases. However, a universal feature is the strong transcript and protein expression of MNX1, a homeobox transcription factor that is normally not expressed in hematopoietic cells. Here, we map the translocation breakpoints on chromosomes 7 and 12 in affected patients to a region proximal to MNX1 and either introns 1 or 2 of ETV6. The frequency of MNX1 overexpression in pediatric AML (n=1556, own and published data) is 2.4% and occurs predominantly in t(7;12)(q36;p13) AML. Chromatin interaction assays in a t(7;12)(q36;p13) iPSC cell line model unravel an enhancer-hijacking event that explains MNX1 overexpression in hematopoietic cells. Our data suggest that enhancer-hijacking may be a more widespread consequence of translocations where no oncofusion product was identified, including e.g. t(1;3) or t(4;12) AML.Copyright © 2024 American Society of Hematology.