The hematopoietic stem cell (HSC) niche is composed of a complex set of stromal support cells that maintain HSCs and promote normal hematopoiesis. We now know that molecular changes within the hematopoietic niche contribute to leukemia development. Leukemia cells often reorganize the hematopoietic niche to promote and support their own survival and growth. Here we will summarize recent works that decipher the normal hematopoietic niche cellular components and describe how the leukemia-transformed niche contributes to hematological malignances. Finally, we will discuss recent publications that highlight a possible role for exosomes in the leukemia-induced niche reorganization. This article is part of a Special Issue entitled: Tumor Microenvironment Regulation of Cancer Cell Survival, Metastasis, Inflammation, and Immune Surveillance edited by Peter Ruvolo and Gregg L. Semenza.
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http://dx.doi.org/10.1016/j.bbamcr.2015.09.017 | DOI Listing |
Adv Exp Med Biol
January 2025
Centre for Diagnostic, Therapeutic and Investigative Studies, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Epigenetic regulation in hematopoietic stem cells (HSCs) research has emerged as a transformative molecular approach that enhances understanding of hematopoiesis and hematological disorders. This chapter investigates the intricate epigenetic mechanisms that control HSCs function, including deoxyribonucleic acid (DNA) methylation, histone modifications, and chromatin remodeling. It also explores the role of non-coding ribonucleic acid (RNAs) as epigenetic regulators, highlighting how changes in gene expression can occur without alterations to the DNA sequence.
View Article and Find Full Text PDFMyelodysplastic syndromes (MDS) are age-related diseases characterized by bone marrow (BM) dysfunction and an increased risk of developing acute leukemia. While there is growing evidence highlighting the crucial role of the BM microenvironment (BMME) in MDS, the specific influence of inflammation on BMME changes, as well as the potential benefits of targeting cytokines therapeutically, remain to be elucidated. We previously found interleukin-1 (IL-1) to be a driver of aging phenotypes of BMME and hematopoietic stem and progenitor cells (HSPCs).
View Article and Find Full Text PDFJ Clin Invest
January 2025
Lindsley F. Kimball Research Institute, New York Blood Center, New York, United States of America.
The bone marrow (BM) niche is critical in regulating hematopoiesis, and sexual dimorphism and its underlying mechanism in BM niche and its impact on hematopoiesis are not well understood. We show that male mice exhibited a higher abundance of leptin-receptor-expressing mesenchymal stromal cells (LepR-MSCs) compared to female mice. Sex-mismatched co-culture and BM transplantation showed that the male BM niche provided superior support for in vitro colony formation and in vivo hematopoietic engraftment.
View Article and Find Full Text PDFCurr Opin Immunol
January 2025
Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences, RIKEN Yokohama Institute, Yokohama, Japan; Division of Integrated High-Order Regulatory Systems, Center for Cancer Immunotherapy and Immunobiology, Kyoto University Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Energy metabolism of immune cells, such as glycolysis and mitochondrial activity, requires strict regulation. This is especially critical in the complex environment of the bone marrow (BM), where there is a need to both preserve the quiescence of hematopoietic stem cells (HSCs) and guarantee timed and effective lineage differentiation of the HSCs. Recent advances highlight the critical roles played by bioactive metabolites in regulating hematopoiesis.
View Article and Find Full Text PDFNat Commun
January 2025
Division of Hematology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Myeloid malignancies are heterogenous disorders characterized by distinct molecular drivers but share convergence of oncogenic signaling pathways and propagation by ripe pro-inflammatory niches. Here, we establish a comprehensive transcriptional atlas across the spectrum of myeloproliferative neoplasms (MPN) and secondary acute myeloid leukemia (sAML) through RNA-sequencing of 158 primary samples encompassing CD34+ hematopoietic stem/progenitor cells and CD14+ monocytes. Supported by mass cytometry (CyTOF) profiling, we reveal aberrant networks of PI3K/AKT/mTOR signalling and NFκB-mediated hyper-inflammation.
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