Expression of Leukemia-Associated Nup98 Fusion Proteins Generates an Aberrant Nuclear Envelope Phenotype
Fig 6
Lamina-associated polypeptide 2α (LAP2α) is altered in Nup98 fusion expressing leukemic cells.
(A) Mouse bone marrow cells were transduced with retroviral particles to express untagged Nup98-HOXA9 and Nup98-HHEX and stained for immunofluorescence microscopy. Expression of these fusion proteins induced lobulations in the NE as evident from the lamin B1 staining (LB1, green). Whereas lamin A/C is not expressed in mouse BM cells (LA/C, magenta), LAP2α (red) is evenly distributed in nuclei from total bone marrow (TBM) cells and lineage minus precursor cells (Lin-), it is diminished from the nucleoplasm and aggregates at the nuclear periphery of mouse BM cells expressing Nup98-HHEX and Nup98-HOXA9, respectively. Electron micrographs of mouse bone marrow cells transduced with (B) Nup98-HHEX and (C) Nup98-HOXA9. Scale bars, 2 μm (C); 1 μm (B). (D) Lamin B1 staining of patient-derived bone marrow cells revealed irregular NE contour. Lamin A/C is not consistently expressed in patient cells and LAP2α is diminished from the nucleoplasm and aggregates at the nuclear periphery. Patient 1 harbored a Nup98-RAP1GDS1, patient 2 a Nup98-NSD1, and patient 3 a Nup98-DDX10 fusion, respectively. Scale bars, 10 μm.