2017年1月9日 · We here explored this issue using an inducible mixed lineage leukemia-eleven nineteen leukemia (MLL-ENL) mouse model. Although multiple progenitor cell types with myeloid potential are potent AML...

In this review, we will discuss the normal biological roles of MLL1 and its fusion partners, how these roles are hypothesized to be dysregulated in the context of MLL1 rearrangements, and the clinical manifestations of this group of leukemias.

2022年11月26日 · We found the YEATS domain is retained in 84.1% of MLL-ENL patients and crucial for MLL-ENL-mediated leukemogenesis in mouse models. Mechanistically, deletion of the YEATS domain impaired...

MLL基因（myeloid/lymphoid leukemia或mixed lineage leukemia）也称为ALL1（acute lymphocytic leukemia 1）或HRX（homolog of trithorax），具有三个区域与果蝇三胸蛋白同源。累及MLL基因的白血病既可见于ALL，也可见于AML。见于AML的MLL异常，除MLL-PTD主要见于M1和M2外，其他的MLL融合基因 ...

他们发现，ENL 的失活削弱了 MLL-r 细胞中 SEC 和 DotCom 的功能。 ENL 与 SEC、DotCom 结合的能力提示了一种模型——ENL 通过 YEATS 结构域，识别乙酰化 H3，增强 SEC 和 DotCom 复合体与 DNA 结合的稳定性，并调节基因组异常区域的活性（图 1）。

2024年10月29日 · We propose MLL oncoproteins promote lineage-switching events through dynamic chromatin binding at lineage-specific target genes, and may support resistance to menin inhibitors through similar...

ENL is a histone acetylation reader and a critical component of the super elongation complex. ENL plays pivotal roles in the regulation of chromatin remodelling and gene expression of many important proto-oncogenes, such as Myc, Hox genes, via histone acetylation.

2020年11月5日 · In this study, we investigate the clinical relevance and leukemic importance of the ENL YEATS domain in MLL-ENL leukemias. We first analyzed t (11;19) (MLL-ENL) patient data to determine the sites of chromosomal translocation within the ENL gene.

2017年6月1日 · We here explored this issue using an inducible mixed lineage leukemia-eleven nineteen leukemia (MLL-ENL) mouse model. Although multiple progenitor cell types with myeloid potential are potent AML leukemia-initiating cells, also the earliest lymphoid progenitors were capable of initiating AML.

2024年6月3日 · In this study we investigated the expression of human MLL-ENL and MLL-AF9 in the myeloid lineage of zebrafish embryos. We observed an expansion of MLL positive cells and determined these cells colocalized with the myeloid markers spi1b, mpx, and mpeg.

2022年1月15日 · MLLT3 and MLLT1 drive protein-protein interactions via coupled binding and folding. Fusion proteins (MLL-AF9 and MLL-ENL) with MLL are drivers of leukemia. Inhibitors of the intrinsically disordered AF9 AHD protein-protein interactions. Mutations in MLLT1 drive Wilms tumor via enhanced phase separation & transcription.

2024年3月30日 · We reveal that fetal MLL::ENL -expressing lymphomyeloid multipotent progenitors (LMPPs) are intrinsically programmed towards a lymphoid fate but give rise to myeloid leukemia in vivo,...

2018年6月12日 · The authors established a doxycycline (DOX)-inducible transgenic mouse model "iMLL-ENL" in which induction in long-term hematopoietic stem cells, lymphoid primed multipotent progenitor cells, multipotent progenitors (MPP4) but not in more committed myeloid granulocyte-macrophage progenitors led to a fully reversible acute leukemia expressing ...

AF9 和 ENL 是混合谱系白血病（Mixed lineage leukemia， MLL）染色体异位发生基因融合的常见伙伴基因，由此引发的白血病在幼儿病患中很常见且比较恶性，预后效果较差。

2016年4月12日 · Here we report a strategy that identifies primary target genes of a conditionally transforming MLL-ENL protein that was created by insertion of a fusion of human ENL cDNA linked to a tamoxifen-inducible estrogen receptor into the mouse Mll locus (henceforth abbreviated MLL-ENL) (Takacova et al., 2012). By nascent RNA sequencing (RNA-seq), in ...

2018年5月18日 · Functional investigation of 128 conserved MLL-fusion-interactors identifies a specific role for the lysine methyltransferase SETD2 in MLL-leukemia. SETD2 loss causes growth arrest and...

为在全基因组水平阐明MLL-ENL蛋白如何通过调节微RNA表达异常而导致血癌发生，本项目利用染色质免疫共沉淀结合高通量测序，在可诱导激活MLL-ENL融合蛋白的小鼠细胞中，鉴定被MLL-ENL蛋白结合并能促进下游转录的DNA序列。 同时，综合微RNA表达谱测序结果，确定直接受MLL-ENL蛋白调控后表达升高的关键微RNA，并进一步明确其靶基因。 由此形成以微RNA为中心，从转录因子对微RNA的调控、到微RNA对靶基因调节的网络，将染色体易位这一遗传学改 …

2020年3月16日 · Here, we take advantage of cells conditionally blocked at the multipotent haematopoietic progenitor stage to develop a MLL-r model capturing early cellular and molecular consequences of MLL-ENL...

MLL is a methyltransferase that is involved in the positive regulation of Hox gene expression and methylation of histone H3 lysine residue 4 (H3K4). As a result of inter-chromosomal...

1 天前 · Mueller, D. et al. A role for the MLL fusion partner ENL in transcriptional elongation and chromatin modification. Blood 110, 4445–4454 (2007).