The pathogenesis of mixed-lineage leukemia.

The pathogenesis of mixed-lineage leukemia.
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DOI:
10.1146/annurev-pathol-011811-132434
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发表时间:
2012
期刊:
Annual review of pathology
影响因子:
--
通讯作者:
Hess JL
Hess JL
中科院分区:
其他
文献类型:
--
作者:
Muntean AG;Hess JL

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侵袭性白血病在儿童和成人中都是由于位于染色体11q23上的混合谱系白血病(MLL)基因重排而引起的。MLL基因编码一个大的组蛋白甲基转移酶,直接结合并积极调节基因转录,包括HOX基因。MLL参与染色体易位、部分串联重复和扩增,所有这些都由于持续的HOX表达和停滞的分化而导致造血系统恶性肿瘤。MLL病变与急性髓性白血病(AML)和急性淋巴细胞白血病(ALL)相关,并且通常与相对较差的预后相关,尽管改善了治疗方案,如异基因造血干细胞移植,强调了对新治疗方案的需求。最近的进展已经开始揭示驱动MLL相关白血病的分子机制,这为治疗开发提供了机会。在这里,我们讨论MLL白血病的病因和治疗发展的潜在方向。
Aggressive leukemias arise in both children and adults as a result of rearrangements to the Mixed Lineage Leukemia (MLL) gene located on chromosome 11q23. The MLL gene encodes a large histone methyltransferase that directly binds and positively regulates gene transcription including HOX genes. MLL is involved in chromosomal translocations, partial tandem duplication 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 (AML) and acute lymphoid leukemia (ALL) and are usually associated with a relatively poor prognosis despite improved treatment options like allogeneic hematopoietic stem cell transplantation underscoring the need for new treatment regimens. Recent advances have begun to reveal the molecular mechanisms driving MLL associated leukemias which have provided opportunities for therapeutic development. Here we discuss the etiology of MLL leukemias and potential directions for therapeutic development.
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