Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Annu Rev Pathol. 2012;7:283-301. doi: 10.1146/annurev-pathol-011811-132434. Epub 2011 Oct 17.
Aggressive leukemias arise in both children and adults as a result of rearrangements to the mixed-lineage leukemia gene (MLL) located on chromosome 11q23. MLL encodes a large histone methyltransferase that directly binds DNA and positively regulates gene transcription, including homeobox (HOX) genes. MLL is involved in chromosomal translocations, partial tandem duplications, and amplifications, all of which result in hematopoietic malignancies due to sustained HOX expression and stalled differentiation. MLL lesions are associated with both acute myeloid leukemia and acute lymphoid leukemia and are usually associated with a relatively poor prognosis despite improved treatment options such as allogeneic hematopoietic stem cell transplantation, which underscores the need for new treatment regimens. Recent advances have begun to reveal the molecular mechanisms that drive MLL-associated leukemias, which, in turn, have provided opportunities for therapeutic development. Here, we discuss the etiology of MLL leukemias and potential directions for future therapy.
侵袭性白血病可在儿童和成人中由于混合谱系白血病基因（MLL）位于 11q23 染色体上的重排而发生。MLL 编码一种大型组蛋白甲基转移酶，可直接结合 DNA 并正向调节基因转录，包括同源盒（HOX）基因。MLL 参与染色体易位、部分串联重复和扩增，所有这些都会由于持续的 HOX 表达和分化停滞导致造血恶性肿瘤。MLL 病变与急性髓系白血病和急性淋巴细胞白血病都有关，尽管有改善的治疗选择，如异体造血干细胞移植，但预后通常较差，这突显了需要新的治疗方案。最近的进展开始揭示驱动 MLL 相关白血病的分子机制，这反过来又为治疗开发提供了机会。在这里，我们讨论了 MLL 白血病的病因和未来治疗的潜在方向。
