Academic Journal
Aging-driven reprogramming of CD34⁺ hematopoietic stem cells in leukemogenesis: Mechanisms and therapeutic implications.
| Τίτλος: | Aging-driven reprogramming of CD34⁺ hematopoietic stem cells in leukemogenesis: Mechanisms and therapeutic implications. |
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| Συγγραφείς: | Pandey SN; Department of Pharmacology, Teerthanker Mahaveer College of Pharmacy, Teerthanker Mahaveer University, Moradabad, Uttar Pradesh 244001, India., Afzal M; Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, Jeddah 21442, Saudi Arabia., Rekha A; Dr DY Patil Medical College, Hospital and Research Centre, Pimpri, Pune, India., Vijayan MP; Faculty of Health Sciences, Villa College, Maldives., Uniyal P; Faculty of Pharmacy, Graphic Era Hill University, Dehradun, India; Centre for Promotion of Research, Graphic Era Deemed University, Dehradun, India., Maji C; Noida Institute of Engineering and Technology (Pharmacy Institute), 19 Knowledge Park 2, Greater Noida, India., Khan A; Center For Health Research, Northern Border University, Arar 73213, Saudi Arabia., Thangavelu L; Faculty of Health Sciences, Villa College, Maldives., Nagaraj K; Department of General Medicine, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha Nagar, Thandalam, Kanchipuram - Chennai Rd., Chennai, Tamil Nadu 602105, India. Electronic address: nagarajk.smc@saveetha.com. |
| Πηγή: | Mechanisms of ageing and development [Mech Ageing Dev] 2026 Aug; Vol. 232, pp. 112212. Date of Electronic Publication: 2026 Jun 11. |
| Τύπος έκδοσης: | Journal Article; Review |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Science Ireland Country of Publication: Ireland NLM ID: 0347227 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-6216 (Electronic) Linking ISSN: 00476374 NLM ISO Abbreviation: Mech Ageing Dev Subsets: MEDLINE |
| Imprint Name(s): | Publication: Limerick : Elsevier Science Ireland Original Publication: Lausanne, Elsevier Sequoia. |
| Ιατρικοί όροι (MeSH): | Hematopoietic Stem Cells*/metabolism , Hematopoietic Stem Cells*/pathology , Antigens, CD34*/metabolism , Aging*/pathology , Aging*/metabolism , Leukemia*/pathology , Leukemia*/metabolism , Leukemia*/therapy , Neoplastic Stem Cells*/pathology , Neoplastic Stem Cells*/metabolism , Cell Transformation, Neoplastic*/metabolism , Cell Transformation, Neoplastic*/pathology , Cellular Senescence* , Cellular Reprogramming*, Humans ; Animals |
| Περίληψη: | Aging is a major driver of hematological impairment and a significant risk factor for hematologic malignancies. CD34⁺ hematopoietic stem and progenitor cells (HSPCs) represent a critical cellular compartment in which age-related changes converge to promote leukemogenesis. This review synthesizes contemporary findings on the interplay between intrinsic hallmarks of aging, including genomic instability, telomere attrition, epigenetic drift, and mitochondrial dysfunction, and extrinsic factors, including chronic inflammation and bone marrow niche remodeling, in the reprogramming of CD34⁺ cell fate. These alterations promote clonal hematopoiesis of indeterminate potential (CHIP), impair immune competence, and increase susceptibility to malignant transformation. Special attention is directed towards CD34⁺CD38⁻ subsets, which possess leukemic stem cell (LSC) functionality and demonstrate resistance to standard treatments. Emerging biomarkers, including CD123, CD96, IL1RAP, and CD133, are discussed in relation to disease progression and therapeutic targeting. We emphasize how aging-related inflammatory signaling and metabolic changes preferentially benefit pre-leukemic clones. Ultimately, we investigate therapeutic approaches designed to disrupt leukemogenesis by focusing on aging mechanisms, the senescent microenvironment, and vulnerabilities specific to leukemic stem cells (LSCs). This review contextualizes CD34⁺ cell biology within aging mechanisms, offering a cohesive view on illness onset and highlighting prospects for early intervention in older populations. (Copyright © 2026 Elsevier B.V. All rights reserved.) |
| Contributed Indexing: | Keywords: Aging; CD34(+) cells; Clonal hematopoiesis; Hematopoietic stem cells; Leukemic stem cells; Leukemogenesis |
| Substance Nomenclature: | 0 (Antigens, CD34) |
| Entry Date(s): | Date Created: 20260611 Date Completed: 20260708 Latest Revision: 20260708 |
| Update Code: | 20260709 |
| DOI: | 10.1016/j.mad.2026.112212 |
| PMID: | 42276300 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1872-6216 |
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| DOI: | 10.1016/j.mad.2026.112212 |