ArticleScience translational medicine2022
CKS1 inhibition depletes leukemic stem cells and protects healthy hematopoietic stem cells in acute myeloid leukemia.
Article in Science translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 21 citations in OpenAlex.
- Integrated analysis of post-transcriptional regulations reveals insights into acute myeloid leukemia.Communications biology · 2025Article
- How to drug a leukemic stem cell: deciphering heterogeneity for better specificity.Blood neoplasia · 2025Review
- Assessment of structural and activity-related contributions of various PIM-1 kinase inhibitors in the treatment of leukemia and prostate cancer.Molecular diversity · 2025Review
- Review
- Kinome profiling reveals pathogenic variant specific protein signalling networks in MEN2 children with Medullary Thyroid Cancer.NPJ precision oncology · 2025Article
- PSPC1 exerts an oncogenic role in AML by regulating a leukemic transcription program in cooperation with PU.1.Cell stem cell · 2025Article
- Differential inflammatory conditioning of the bone marrow by acute myeloid leukemia and its impact on progression.Blood advances · 2024Article
- The AC010247.2/miR-125b-5p axis triggers the malignant progression of acute myelocytic leukemia by IL-6R.Heliyon · 2024Article
- CKS1B as a potential target for prognostic assessment and intervention in pancreatic cancer and its role in abnormal proliferation and cellular phenotype through mediation of cell cycle signaling pathways.Saudi medical journal · 2024Article
- Research Progress on the Use of Metformin in Leukemia Treatment.Current treatment options in oncology · 2024Review
- Twist family BHLH transcription factor 1 is required for the maintenance of leukemia stem cell in MLL-AF9Haematologica · 2024Article
- Recent Advances in Natural Products with Anti-Leukemia and Anti- Lymphoma Activities.Mini reviews in medicinal chemistry · 2024Review
- Immunodeficient NBSGW mouse strain allows chemotherapy modeling in AML patient-derived xenografts.HemaSphere · 2024Article
- Hydrogel Cross-Linking via Thiol-Reactive Pyridazinediones.Biomacromolecules · 2023Article
- Sox13 and M2-like leukemia-associated macrophages contribute to endogenous IL-34 caused accelerated progression of acute myeloid leukemia.Cell death & disease · 2023Article
- The CKS1/CKS2 Proteostasis Axis Is Crucial to Maintain Hematopoietic Stem Cell Function.HemaSphere · 2023Article
- PD-1 signalling defines and protects leukaemic stem cells from T cell receptor-induced cell death in T cell acute lymphoblastic leukaemia.Nature cell biology · 2023Article
- Markers for human haematopoietic stem cells: The disconnect between an identification marker and its function.Frontiers in physiology · 2022Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Acute myeloid leukemia (AML) is an aggressive hematological disorder comprising a hierarchy of quiescent leukemic stem cells (LSCs) and proliferating blasts with limited self-renewal ability. AML has a dismal prognosis, with extremely low 2-year survival rates in the poorest cytogenetic risk patients, primarily due to the failure of intensive chemotherapy protocols to deplete LSCs and toxicity of therapy toward healthy hematopoietic cells. We studied the role of cyclin-dependent kinase regulatory subunit 1 (CKS1)-dependent protein degradation in primary human AML and healthy hematopoiesis xenograft models in vivo. Using a small-molecule inhibitor (CKS1i), we demonstrate a dual role for CKS1-dependent protein degradation in reducing patient-derived AML blasts in vivo and, importantly, depleting LSCs, whereas inhibition of CKS1 has the opposite effect on normal hematopoiesis, protecting normal hematopoietic stem cells from chemotherapeutic toxicity. Proteomic analysis of responses to CKS1i in our patient-derived xenograft mouse model demonstrate that inhibition of CKS1 in AML leads to hyperactivation of RAC1 and accumulation of lethal reactive oxygen species, whereas healthy hematopoietic cells enter quiescence in response to CKS1i, protecting hematopoietic stem cells. Together, these findings demonstrate that CKS1-dependent proteostasis is a key vulnerability in malignant stem cell biology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.