有研究通过在人cd34 + 造血干细胞上表达mll-小鼠af4嵌合融合基因，建立了mll-af4 pro-b-all的模型。 表达 MLL - AF 4的细胞表现出对淋巴系别的强烈偏向和对髓系定向的抵抗。

2012年1月31日 · Pre-leukemic MLL-AF4 fusions arise prenatally and typically lead to overt acute lymphoblastic leukemia (ALL) at or shortly after birth. In a recent study, Bueno and colleagues explored the...

2017年1月23日 · In order to define a core set of MLL rearranged targets, we investigated the genome-wide binding of the MLL-AF9 and MLL-AF4 fusion proteins and associated epigenetic signatures in acute...

基因敲除实验提示mll作用于造血干细胞向定向祖细胞发育和扩增的早期造血阶段。 常见的mll融合基因的断裂、融合位点和mll内部串联重复突变结构. 累及mll基因的染色体易位中，已发现80余种基因与mll形成融合基因。

2023年8月25日 · In leukemias controlled by the MLL-AF4 fusion protein, we use the ultra-high resolution technique Micro-Capture-C (MCC) to show that MLL-AF4 binding promotes broad, high-density regions of...

日本国立癌症研究中心于2022年12月13日宣布，发现了由引起恶性度高的白血病的MLL-AF4基因产生RNA，最终抑制蛋白质产生过程的机制。 该研究是由公益财团法人庄内地区产业振兴中心/国立癌症研究中心·鹤冈合作研究据点癌症代谢综合征研究室的横山明彦小组组长、奥田博史研究员（现：横滨市立大学研究生院医学研究科免疫学）等研究小组进行的。 研究成果刊登在“Nature Communications”上。 白血病是年轻人中最常见的癌症，现行的治疗方法有很难治愈的预后不 …

mll基因重排在aml（多为急性单核细胞白血病）中为14%，最常见的是mll-af6和mll-af9；在all中的发生率为6%，最常见的是mll-af4 ，mll-af4罕见于混合型急性白血病及aml-m 0 ，但是mll-af4在amkl中阳性鲜见文献报道。

2017年1月10日 · Understanding the underlying molecular mechanisms of defined cancers is crucial for effective personalized therapies. Translocations of the mixed-lineage leukemia (MLL) gene produce fusion proteins such as MLL-AF4 that disrupt epigenetic pathways and cause poor-prognosis leukemias.

2023年8月25日 · In leukemias controlled by the MLL-AF4 fusion protein, we use the ultra-high resolution technique Micro-Capture-C (MCC) to show that MLL-AF4 binding promotes broad, high-density regions of enhancer-promoter interactions at a subset of key targets.

2016年11月14日 · Here we show that MLL fused to murine Af4, highly conserved with human AF4, produces high-titer retrovirus permitting efficient transduction of human CD34 + cells, thereby generating a model of t (4;11) pro-B acute lymphoblastic leukemia (ALL) that fully recapitulates the immunophenotypic and molecular aspects of the disease.

2016年7月26日 · Using a conditional Mll-AF4-expressing mouse model in which fusion expression is targeted to the earliest definitive hematopoietic cells generated in the mouse embryo, we demonstrate that Mll-AF4 imparts enhanced B lymphoid potential and increases repopulation and self-renewal capacity during a putative pre-leukemic state.

2005年9月16日 · MLL-AF4, an MLL fusion protein that is associated with infant pro-B acute lymphoblastic leukemias, is the most prevalent of the numerous MLL fusion proteins (9), and it is usually associated with a poor prognosis (10). Numerous data show that MLL fusion genes can transform hematopoietic cells in vitro and cause leukemia in vivo (11, 12).

2021年11月25日 · Here, using the most common MLL -r infant-ALL, MLL-AF4, as a disease model, we identify fetal-specific gene expression programs in primary human hematopoietic cells and show that MLL-AF4...

2023年11月16日 · Cellular ontogeny and MLL breakpoint site influence the capacity of MLL- edited CD34 + hematopoietic cells to initiate and recapitulate infant patients' features in pro–B-cell acute lymphoblastic leukemia (B-ALL). We provide key insights into the leukemogenic determinants of MLL-AF4 + infant B-ALL.

2017年6月8日 · In 11q23 leukemias, the N-terminal part of the mixed lineage leukemia (MLL) gene is fused to >60 different partner genes. In order to define a core set of MLL rearranged targets, we investigated the genome-wide binding of the MLL-AF9 and MLL-AF4 fusion proteins and associated epigenetic signature …

在急性白血病治疗过程中系别转化罕见,在与系别转化相关的染色体畸变中,t(4;11)(q21;q23)与KMT2A/AFF1 融合蛋白[原混合谱系白血病(mixed linage leukemia,MLL)基因 MLL/AFF1 或 MLL/AF4 ]重排最为常见[1 ].研究表明,MLL重排急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)起源于一个有 ...

2021年11月25日 · In this issue of Blood, Malouf et al characterize 2 microRNAs (miRNAs) that are effectors of malignant transformation by the MLL-AF4 fusion protein. 1 Mixed lineage leukemia (MLL) gene fusions are the molecular hallmark of infant acute lymphoblastic leukemia (ALL) and are present in tumor cells in up to 80% of patients. 2 Detection of the gene ...

2016年11月14日 · MLL-AF4 leukemia is the predominant infant acute leukemia and has a poor prognosis. No current experimental models accurately reflect the human disease. Lin et al., in this issue of Cancer Cell, describe their model that recapitulates multiple key aspects of this aggressive disease, facilitating future mechanistic and preclinical studies.

2017年1月10日 · Here, we find that at a subset of gene targets, MLL-AF4 binding spreads into the gene body and is associated with the spreading of Menin binding, increased transcription, increased H3K79 methylation (H3K79me2/3), a disruption of normal H3K36me3 patterns, and unmethylated CpG regions in the gene body.

2008年11月4日 · The report by Armstrong and colleagues (Krivtsov et al., 2008) provides novel insights into MLL-AF4 pathogenesis but also raises two longstanding and unanswered questions: (1) What determines the lineage specificity of MLL, and (2) can we target epigenetic enzymes that associate with MLL fusions for leukemogenic suppression?