biostudies-literatureUnknown136(2)Niederkorn MMyelodysplastic syndromes (MDSs) are malignant hematopoietic stem and progenitor cell (HSPC) disorders that lead to ineffective blood production with poor outcomes. We previously showed that F-box only protein 11 (FBXO11) is downregulated in MDS, and here we report how this event contributes to disease progression. Integration of multiomics data revealed that the SCF-FBXO11 complex regulates spliceosome and ribosome components in a nucleophosmin 1 (NPM1)-centric network. FBXO11 facilitates the ubiquitylation of NPM1, whereby deletion of FBXO11 results in the reorganization of NPM1 and a de-repression of alternative splicing. Label-free total quantitative proteomics demonstrated that the FBXO11-NPM1 interactome was markedly downregulated in cells from patients with CD34+ MDS. In addition, wThe Journal of clinical investigatione193636https://www.ebi.ac.uk/biostudies/studies/S-EPMC12807477biostudies-literatureFBXO11 suppression rewires an NPM1-centered interactome influencing the progression of myelodysplastic syndrome.PMC12807477Bezavada LCotton APagala VRWu CFu YVerma ANiederkorn MKang GPruett-Miller SMZhai JWeiss MPalmer LEXu PKonada LCrispino JDAminov STaylor ABHall TNarina SJi PRampal RKSchieber MSchild AHigh AAJanke LJYuan ZFSteele JAMcGovern EGurbuxani SfalseFBXO11 suppression rewires an NPM1-centered interactome influencing the progression of myelodysplastic syndrome.Myelodysplastic syndromes (MDSs) are malignant hematopoietic stem and progenitor cell (HSPC) disorders that lead to ineffective blood production with poor outcomes. We previously showed that F-box only protein 11 (FBXO11) is downregulated in MDS, and here we report how this event contributes to disease progression. Integration of multiomics data revealed that the SCF-FBXO11 complex regulates spliceosome and ribosome components in a nucleophosmin 1 (NPM1)-centric network. FBXO11 facilitates the ubiquitylation of NPM1, whereby deletion of FBXO11 results in the reorganization of NPM1 and a de-repression of alternative splicing. Label-free total quantitative proteomics demonstrated that the FBXO11-NPM1 interactome was markedly downregulated in cells from patients with CD34+ MDS. In addition, w2026-01-01T00:00:00Z2026 Jan2026-07-15T06:35:11.415Z2026-06-30T03:21:57.837ZS-EPMC128074774154276610.1172/JCI193636