Sep 10, 2018 · 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.

Oct 8, 2020 · Because pharmacologic XPO1 inhibition also potently downregulates HOX expression in NPM1-mutated AML, 74 we envision synchronized inhibition of menin-MLL and XPO1 as an appealing therapeutic option to block HOX/MEIS expression in NPM1-mutated AML.

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.

Mar 7, 2024 · 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.

Perhaps NPM1 mutation directly influences HOX expression or possibly, NPM1 mutation leads to the arrested development of hematopoeitic precursors at a primitive stage at which HOX expression is elevated.

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.

Oct 8, 2020 · NPM1 mutations represent the most common genetic lesion in adult acute myeloid leukemia (AML; about one third of cases), and they act deterministically to cause the aberrant cytoplasmic delocalization of NPM1 mutants.

Jun 11, 2019 · 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.

Aug 25, 2022 · We also discuss the current therapeutic results obtained in NPM1 -mutated AML with the BCL-2 inhibitor venetoclax and the preliminary clinical results using menin inhibitors targeting...

Oct 23, 2024 · In this study, we investigated the subcellular localization and leukemogenic potential of two rare NPM1-fusion proteins, NPM1::MLF1 and NPM1::CCDC28A. NPM1::MLF1 is present in both the nucleus...