2018年9月10日 · Here, we show that loss of NPM1c from the cytoplasm, either through nuclear relocalization or targeted degradation, results in immediate downregulation of homeobox (HOX) genes followed by differentiation.

2024年3月7日 · In this review we summarize molecular mechanisms underlying HOX regulation in clinical subsets of AML, with a focus on NPM1 mutated (NPM1 mut) AML comprising a third of all AML patients.

2024年10月23日 · Mechanistically, both NPM1-fusions bind to the HOX gene cluster and, like NPM1c, cause aberrant upregulation of HOX genes in cooperation with XPO1. The XPO1 inhibitor selinexor suppressed...

2023年6月26日 · Here, we report that NPM1C+ activates signature HOX genes and reprograms cell cycle regulators by altering CTCF-driven topologically associated domains (TADs).

2024年10月24日 · The XPO1 inhibitor selinexor suppressed HOX activation and colony formation driven by the NPM1-fusions. NPM1::CCDC28A cells were also sensitive to menin inhibition. Thus, our study provides experimental evidence that both NPM1::MLF1 and NPM1::CCDC28A are oncogenes with functions similar to NPM1c.

2019年11月1日 · Higher expression of the HOX genes was identified in tumors harboring NPM1 gene mutations by computationally linking genotype and gene expression. In vitro validation of these genes supports their potential therapeutic application in AML.

This review summarizes features of mutant NPM1-related disease, with a particular emphasis on recent discoveries relevant to disease monitoring, prognostication, and therapeutic intervention. Recent findings: Recent studies have shown that HOX/MEIS gene overexpression is central to the survival of NPM1-mutated cells.

他和团队通过基因工程化的细胞系和小鼠模型研究发现， NPM1 突变蛋白（NPM1c）能够结合到染色质上，并且可以直接调控 Hox 基因。 图｜基于小鼠模型探索 XPO1 和 Menin 抑制剂 联合用药治疗 NPM1c 白血病（来源： Cancer Discovery） 传统观点通常认为 NPM1 突变蛋白从细胞核仁转移到细胞浆内可能会抑制 Hox 基因表达。 “然而我们的发现正好相反， NPM1 突变蛋白可以直接结合在基因组区段并劫持转录，导致 Hox 基因的转录无法停止。 ” 他指出。 “我们通过这项研 …

2018年9月10日 · NPM1 mutations are among the most common genetic events in AML and their role in leukemogenesis is still obscure. Here, we show that HOX expression, differentiation levels, and cell growth of AML cells are dependent on mutant NPM1 and its …

Brunetti et al. show that specific loss of NPM1c from the cytoplasm leads to downregulation of HOX genes and differentiation in NPM1 mutant AML. Blocking NPM1c nuclear export by XPO1 inhibition reduces cytoplasmic NPM1c, promotes AML differentiation, and prolongs the survival of a mouse model of NPM1c + AML.