KMT2A是抑癌基因，编码蛋白是组蛋白甲基转移酶MLL1，一种表观遗传调节剂，甲基化组蛋白H3（H3K4）尾部的赖氨酸残基4。H3K4的甲基化导致基因组的可接触性增加，转录复合物的募集，以及基因表达的激活。MLL1通过刺激包括同源框（Hox）基因在内的几种重要发育基因的表达，对胚胎发生和正常造血至关重要。在儿童/成人急性髓系白血病（AML）和急性淋巴细胞白血病（ALL）中，已经确定KMT2A发生染色体易位导致获得功能性的融合蛋白MLL1；并且在治疗相关的AML中MLL1呈现过表达。尽管KMT2A在白血病中与多种基因发生融合，但最常见的KMT2A融合基因是AF4，AF9和ENL，它们是与转录延伸机制相互作用的蛋白质。MLL1融合蛋白破坏造血干细胞的正常活性和正常的染色质状态，导致致癌信号通路的激活。此外，MLL1的功能缺失突变在实体肿瘤包括膀胱癌、胃癌和子宫内膜癌中已被鉴定。

KMT2A encodes the histone methyltransferase MLL1, an epigenetic modulator that methylates lysine residue 4 on the tail of histone H3 (H3K4). Methylation of H3K4 leads to increased genome accessibility, recruitment of transcriptional complexes, and activation of gene expression. MLL1 is crucial for embryogenesis and normal hematopoiesis by stimulating expression of several important developmental genes including the homeobox (Hox) genes. Chromosomal translocations involving MLL1 that result in gain-of-function fusion proteins have been identified in pediatric and adult acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) and are overrepresented in therapy-related AML. Though KMT2A has a diverse group of fusion partners in leukemia, the most common KMT2A recombination partners include AF4, AF9, and ENL, which are proteins that interact with transcriptional elongation machinery. MLL1 fusion proteins disrupt the normal activity of hematopoietic stem cells and the normal chromatin state, leading to activation of oncogenic signaling pathways. In addition, loss-of-function mutations in KMT2A have been identified in solid tumors including bladder, stomach and endometrial cancers. DOT1L inhibitors, which are currently being tested in clinical trials, have been shown to have activity against KMT2A-rearranged leukemias.

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