Hematopoietic stem cells (HSC) must balance self-renewal and differentiation to provide sufficient primitive cells to sustain hematopoiesis, while generating more mature cells with specialized capabilities. The enhanced self-renewal capacity of primitive HSCs enables their ability to sustain hematopoiesis throughout decades of life and their ability to repopulate a host when used therapeutically in bone marrow transplantation. However, hematopoietic cell perturbations resulting in unchecked self-renewal participate in leukemogenesis. While mechanisms governing self-renewal are still being uncovered, they are thought to bear relationship to the malignant process in a variety of tumor types and may therefore provide useful therapeutic targets in putative cancer stem cells. This review discusses molecular mechanisms recently defined to participate in HSC governance and highlights features of stem cell interactions with the microenvironment that may help guide therapies directed at HSCs.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1038/sj.leu.2403515 | DOI Listing |
iScience
January 2025
INSERM U1287, Université Paris-Saclay, Gustave Roussy Cancer Center, Villejuif, France.
Elevated circulating levels of calprotectin (CAL), the S100A8/A9 heterodimer, are biomarkers of severe systemic inflammation. Here, we investigate the effects of CAL on early human hematopoiesis. CAL demonstrates limited impact on gene expression in stem and progenitor cells, in contrast with interleukin-6 (IL6), which promotes the expression of the and genes in hematopoietic progenitors and the generation of monocytes that release CAL.
View Article and Find Full Text PDFiScience
January 2025
Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
ETV2/ER71, an ETS (E-twenty six) transcription factor, is critical for hematopoiesis and vascular development. However, research about the molecular mechanisms behind ETV2-mediated gene transcription is limited. Herein, we demonstrate that ETV2 and KDM4A, an H3K9 demethylase, regulate hematopoietic and endothelial genes.
View Article and Find Full Text PDFMol Ther Nucleic Acids
March 2025
Comprehensive Bone Marrow Failure Center, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Fanconi anemia (FA) is a congenital multisystem disorder characterized by early-onset bone marrow failure (BMF) and cancer susceptibility. While gene addition and repair therapies are being considered as treatment options, depleted hematopoietic stem cell (HSC) pools, poor HSC mobilization, compromised survival during transduction, and increased sensitivity to conventional conditioning strategies limit eligibility for FA patients to receive gene therapies. As an alternative approach, we explored protein replacement by mRNA delivery via lipid nanoparticles (LNPs).
View Article and Find Full Text PDFCureus
December 2024
Cellular Therapy Department, Instituto Português de Oncologia do Porto Fernando Gentil, Entidades Públicas Empresariais (EPE), Porto, PRT.
Acute lymphoblastic leukemia (ALL) poses a significant challenge due to its high relapse rate despite initial chemotherapy. Cell therapy plays an important and promising role in refractory ALL cases. The aim is to present a complex case of a 20-year-old male patient with relapsed ALL and to explore the different therapeutic options of cellular therapy - allogeneic hematopoietic stem cell transplantation, donor lymphocyte infusion, and chimeric antigen receptor T - detailing the collection, processing, and infusion, as well as the associated complications and management strategies.
View Article and Find Full Text PDFFront Cell Dev Biol
December 2024
Biomedical Research Institute of Southern California, Oceanside, CA, United States.
Interferon types-I/II (IFN-αβ/γ) secretions are well-established antiviral host defenses. The human immunodeficiency virus (HIV) particles are known to prevail following targeted cellular interferon secretion. CD4 T-lymphocytes are the primary receptor targets for HIV entry, but the virus has been observed to hide (be latent) successfully in these cells through an alternate entry route via interactions with LFA1.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!