ArticleNature communications2018
Restricted cell cycle is essential for clonal evolution and therapeutic resistance of pre-leukemic stem cells.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Targeting LMO2-induced autocrine FLT3 signaling to overcome chemoresistance in early T-cell precursor acute lymphoblastic leukemia.Leukemia · 2025Article
- Tet2 is a tumor suppressor in the preleukemic phase of T-cell acute lymphoblastic leukemia.Blood advances · 2024Article
- Interspecies interactions in dairy biofilms drive community structure and response against cleaning and disinfection.Biofilm · 2024Article
- Article
- Stem cell-like reprogramming is required for leukemia-initiating activity in B-ALL.The Journal of experimental medicine · 2024Article
- Subclones of bone marrow CD34Cancer · 2022Article
- Cyclin-dependent kinase inhibitors in malignant hematopoiesis.Frontiers in oncology · 2022Review
- Quinacrine-CASIN combination overcomes chemoresistance in human acute lymphoid leukemia.Nature communications · 2021Article
- Oncogene-Induced Reprogramming in Acute Lymphoblastic Leukemia: Towards Targeted Therapy of Leukemia-Initiating Cells.Cancers · 2021Review
- Small molecule inhibition of Dynamin-dependent endocytosis targets multiple niche signals and impairs leukemia stem cells.Nature communications · 2020Article
- E35 ablates acute leukemia stem and progenitor cells in vitro and in vivo.Journal of cellular physiology · 2020Article
- B7-H3 promotes the cell cycle-mediated chemoresistance of colorectal cancer cells by regulating CDC25A.Journal of Cancer · 2020Article
- Leukemia Stem Cells in the Pathogenesis, Progression, and Treatment of Acute Myeloid Leukemia.Advances in experimental medicine and biology · 2019Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pre-leukemic stem cells (pre-LSCs) give rise to leukemic stem cells through acquisition of additional gene mutations and are an important source of relapse following chemotherapy. We postulated that cell-cycle kinetics of pre-LSCs may be an important determinant of clonal evolution and therapeutic resistance. Using a doxycycline-inducible H2B-GFP transgene in a mouse model of T-cell acute lymphoblastic leukemia to study cell cycle in vivo, we show that self-renewal, clonal evolution and therapeutic resistance are limited to a rare population of pre-LSCs with restricted cell cycle. We show that proliferative pre-LSCs are unable to return to a cell cycle-restricted state. Cell cycle-restricted pre-LSCs have activation of p53 and its downstream cell-cycle inhibitor p21. Furthermore, absence of p21 leads to proliferation of pre-LSCs, with clonal extinction through loss of asymmetric cell division and terminal differentiation. Thus, inducing proliferation of pre-LSCs represents a promising strategy to increase cure rates for acute leukemia.
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