CSE1L enrichment in pediatric and young adult acute myeloid leukemia reveals a ribosomal export dependency
Proteins shuttle between the nucleus and cytoplasm through the nuclear pore and via nuclear transport receptors, termed importins and exportins. Although genetic alterations involving nucleoporins are enriched in pediatric, adolescent, and young adult (AYA) acute myeloid leukemia (AML), nucleocytoplasmic transport has not been extensively studied in this disease. We discover that genes encoding nucleocytoplasmic transport pathway components (Kyoto Encyclopedia of Genes and Genomes [KEGG]: hsa03013) are enriched in AML cells from younger patients (≤40 years). Within this pathway, CSE1L is the highest expressed exportin in pediatric/AYA AML and shows minimal expression in hematopoietic stem cells (HSCs). CSE1L depletion reduces leukemic cell growth, proliferation, and clonogenic capacity, targeting leukemia stem cells while sparing normal HSCs. Mechanistically, we identify a novel Ran-GTP-dependent role for CSE1L in regulating pre-60S ribosomal subunit export in AML. Collectively, these data identify nucleocytoplasmic transport and ribosomal subunit export as enriched dependencies in pediatric/AYA AML and establish CSE1L-mediated export as a leukemic vulnerability.
Authors
- Grace Egan (ORCID: https://orcid.org/0000-0002-4036-8403)
- Chaitra Sarathy (ORCID: https://orcid.org/0000-0003-1115-4323)
- Véronique Voisin (ORCID: https://orcid.org/0000-0002-3405-9532)
- Steven Mitchell Kornblau (ORCID: https://orcid.org/0000-0002-5990-9548)
- Yulia Jitkova (ORCID: https://orcid.org/0000-0003-1252-0604)
- Rose Hurren
- Suraj Bansal (ORCID: https://orcid.org/0000-0003-4023-6635)
- Johann K. Hitzler (ORCID: https://orcid.org/0000-0003-1158-186X)
- Geethu Emily Thomas (ORCID: https://orcid.org/0000-0002-8737-1394)
- Amit Kumar (ORCID: https://orcid.org/0000-0002-7398-0498)
- Aaron David Schimmer (ORCID: https://orcid.org/0000-0003-4023-3899)
- Fieke W. Hoff (ORCID: https://orcid.org/0000-0002-7128-1255)
- Nathan Duong (ORCID: https://orcid.org/0000-0001-7171-5554)
- Andy G.X. Zeng (ORCID: https://orcid.org/0000-0002-3223-6400)
- Dakai Ling
- Yongran Yan (ORCID: https://orcid.org/0009-0005-7337-4331)
- John Edgar Dick (ORCID: https://orcid.org/0000-0002-9527-8317)
- Ali Chegini (ORCID: https://orcid.org/0009-0007-8249-7258)
- Dilshad Khan
- Yue Feng
Institutions
- Ontario Institute for Cancer Research (CA)
- University Health Network (CA)
- The University of Texas MD Anderson Cancer Center (US)
- University of Toronto (CA)
- Hospital for Sick Children (CA)
- Princess Margaret Cancer Centre (CA)
- Donnelly Centre for Cellular and Biomolecular Research (CA)
Publication Details
- Journal
- Cell Reports
- Published
- 2026-10-29
- DOI
- https://doi.org/10.1016/j.celrep.2026.118226
- Primary Topic
- Acute Myeloid Leukemia Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Rally Foundation
- Leukemia and Lymphoma Society of Canada
- Ontario Institute for Cancer Research
- Garron Family Cancer Centre