Over the last 15 years the Diagnostic Center of Acute Leukemia (DCAL) at the Frankfurt University has diagnosed and elucidated the Mixed Lineage Leukemia (MLL) recombinome with >100 MLL fusion partners. When analyzing all these different events, balanced chromosomal translocations were found to comprise the majority of these cases (~70%), while other types of genetic rearrangements (3-way-translocations, spliced fusions, 11q inversions, interstitial deletions or insertion of chromosomal fragments into other chromosomes) account for about 30%. In nearly all those complex cases, functional fusion proteins can be produced by transcription, splicing and translation. With a few exceptions (10 out of 102 fusion genes which were per se out-of-frame), all these genetic rearrangements produced a direct MLL fusion gene, and in 94% of cases an additional reciprocal fusion gene. So far, 114 patients (out of 2454 = ~5%) have been diagnosed only with the reciprocal fusion allele, displaying no MLL-X allele. The fact that so many MLL rearrangements bear at least two fusion alleles, but also our findings that several direct MLL fusions were either out-of-frame fusions or missing, raises the question about the function and importance of reciprocal MLL fusions. Recent findings also demonstrate the presence of reciprocal MLL fusions in sarcoma patients. Here, we want to discuss the role of reciprocal MLL fusion proteins for leukemogenesis and beyond.

中文翻译：

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MLL融合的互惠世界：个人观点。

在过去的15年中，法兰克福大学的急性白血病诊断中心（DCAL）已诊断并阐明了具有超过100个MLL融合伙伴的混合谱系白血病（MLL）重组组。分析所有这些不同事件时，发现平衡的染色体易位构成了大多数病例（约70％），而其他类型的基因重排（3向易位，剪接融合，11q倒位，间质缺失或染色体插入）碎片进入其他染色体）约占30％。在几乎所有这些复杂的情况下，功能性融合蛋白均可通过转录，剪接和翻译产生。除了少数例外（102个融合基因中有10个本身是不合框架的），所有这些基因重排均产生了直接的MLL融合基因，在94％的病例中，还有一个额外的相互融合基因。到目前为止，仅对等融合等位基因被诊断出114名患者（2454名患者中约5％），未显示MLL-X等位基因。如此多的MLL重排带有至少两个融合等位基因，但我们的发现也发现，几个直接MLL融合要么是框外融合，要么是缺失，这一事实提出了关于互惠MLL融合的功能和重要性的问题。最近的发现还表明肉瘤患者中存在相互的MLL融合。在这里，我们要讨论互易MLL融合蛋白在白血病发生及以后的作用。但是我们的发现也表明，一些直接的MLL融合要么是框架外融合，要么是缺失，这引发了关于互惠MLL融合的功能和重要性的问题。最近的发现还表明肉瘤患者中存在相互的MLL融合。在这里，我们要讨论互易MLL融合蛋白在白血病发生及以后的作用。但是我们的发现也表明，一些直接的MLL融合要么是框架外融合，要么是缺失，这引发了关于互惠MLL融合的功能和重要性的问题。最近的发现还表明肉瘤患者中存在相互的MLL融合。在这里，我们要讨论互易MLL融合蛋白在白血病发生及以后的作用。