ArticleThe Journal of biological chemistry2016
Hematopoietic and Leukemic Stem Cells Have Distinct Dependence on Tcf1 and Lef1 Transcription Factors.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- High expression of LEF1 correlates with poor prognosis in solid tumors, but not blood tumors: a meta-analysis.Bioscience reports · 2020Pooled it
- Lessons in longevity from blood stem cells under protein stress.Trends in cell biology · 2026Review
- Disease-specific epigenetic deregulation of enhancers, transposons, and polycomb targets in acute promyelocytic leukemia.Genome medicine · 2025Article
- Targeting a macrophage stemness factor to mitigate diseases post respiratory viral infection.bioRxiv : the preprint server for biology · 2025Article
- Single-cell multiomics identifies Tcf1 and Lef1 as key initiators of early thymic progenitor fate.Science immunology · 2025Article
- β-Catenin interacts with canonical RBPs including MSI2 to associate with a Wnt signalling mRNA network in myeloid leukaemia cells.Oncogene · 2025Article
- Quantification of intrinsic regulatory factors refines human hematopoietic progenitor definitions and reveals early erythroid lineage priming.Cell reports · 2025Article
- Research Progress of LEF1 Gene in Malignant Tumors.Clinical Medicine Insights. Oncology · 2025Review
- Expression Profiles of Hypoxia-Related Genes of Cancers Originating from Anatomically Similar Locations Using TCGA Database Analysis.Medicines (Basel, Switzerland) · 2023Article
- Unravelling human hematopoietic progenitor cell diversity through association with intrinsic regulatory factors.bioRxiv : the preprint server for biology · 2023Article
- Unveiling the complexity of transcription factor networks in hematopoietic stem cells: implications for cell therapy and hematological malignancies.Frontiers in oncology · 2023Review
- TCF1 in T cell immunity: a broadened frontier.Nature reviews. Immunology · 2022Review
- NR4A1 promotes LEF1 expression in the pathogenesis of papillary thyroid cancer.Cell death discovery · 2022Article
- New routes to eradicating chronic myelogenous leukemia stem cells by targeting metabolism.International journal of hematology · 2021Review
- Ectopic Tcf1 expression instills a stem-like program in exhausted CD8Cellular & molecular immunology · 2021Article
- Somatic Mutations Drive Specific, but Reversible, Epigenetic Heterogeneity States in AML.Cancer discovery · 2020Article
- Article
- DYRK2 controls a key regulatory network in chronic myeloid leukemia stem cells.Experimental & molecular medicine · 2020Review
- Article
- Low LEF1 expression is a biomarker of early T-cell precursor, an aggressive subtype of T-cell lymphoblastic leukemia.PloS one · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Hematopoietic and leukemic stem cells (HSCs and LSCs) have self-renewal ability to maintain normal hematopoiesis and leukemia propagation, respectively. Tcf1 and Lef1 transcription factors are expressed in HSCs, and targeting both factors modestly expanded the size of the HSC pool due to diminished HSC quiescence. Functional defects of Tcf1/Lef1-deficient HSCs in multi-lineage blood reconstitution was only evident under competitive conditions or when subjected to repeated regenerative stress. These are mechanistically due to direct positive regulation of Egr and Tcf3 by Tcf1 and Lef1, and significantly, forced expression of Egr1 in Tcf1/Lef1-deficient HSCs restored HSC quiescence. In a preclinical CML model, loss of Tcf1/Lef1 did not show strong impact on leukemia initiation and progression. However, when transplanted into secondary recipients, Tcf1/Lef1-deficient LSCs failed to propagate CML. By induced deletion of Tcf1 and Lef1 in pre-established CML, we further demonstrated an intrinsic requirement for these factors in LSC self-renewal. When combined with imatinib therapy, genetic targeting of Tcf1 and Lef1 potently diminished LSCs and conferred better protection to the CML recipients. LSCs are therefore more sensitive to loss of Tcf1 and Lef1 than HSCs in their self-renewal capacity. The differential requirements in HSCs and LSCs thus identify Tcf1 and Lef1 transcription factors as novel therapeutic targets in treating hematological malignancies, and inhibition of Tcf1/Lef1-regulated transcriptional programs may thus provide a therapeutic window to eliminate LSCs with minimal side effect on normal HSC functions.
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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.