IDP mediated transcriptional stabilization as a cause of AML

项目总结 脑膜瘤-1(MN1)蛋白的高表达在AML中很常见， 并与预后不良有关。MN1在小鼠造血细胞中的强制表达 祖细胞会诱发侵袭性白血病。我们最近发现，主要的相互作用 MN1的合作伙伴是BAF核小体定位复合体。MN1稳定染色质上的BAF。 MN1结合与持续活跃的增强子染色质在调节 造血干/祖细胞计划。耐人寻味的是，MN1的S整个编码框架杂乱无章。我们 假设MN1通过增加多个转录中心过度稳定转录中心而导致AML 低价、低亲和力的相互作用，导致局部高BAF浓度和早期 造血转录因子。更好地了解MN1是如何导致白血病的可能 在传统急性髓细胞白血病失败的患者群体中确定靶向治疗的机会 心理治疗。

PROJECT SUMMARY High expression of the intrinsically disordered protein Meningioma-1 (MN1) is common in AML, and associated with a poor prognosis. Forced expression of MN1 in murine hematopoietic progenitors induces an aggressive leukemia. We recently discovered that the primary interaction partner of MN1 is the BAF nucleosome-positioning complex. MN1 stabilizes BAF on chromatin. MN1 binding is associated with sustained active enhancer chromatin at enhancers regulating a hematopoietic stem/progenitor program. Intriguingly, MN1’s entire coding frame is disordered. We hypothesize that MN1 causes AML by overstabilizing transcriptional hubs by increasing multi- valent, low affinity interactions that result in high local concentrations of BAF and early hematopoietic transcription factors. A better understanding of how MN1 causes leukemia may identify opportunities for targeted therapies in a patient population who is failing conventional AML therapy.