Autophagy is a critical cellular process that maintains homeostasis by recycling damaged or aberrant components. This process is orchestrated by a network of proteins that form autophagosomes, which engulf and degrade intracellular material. In cancer, autophagy plays a dual role: it suppresses tumor initiation in the early stages but supports tumor growth and survival in advanced stages. Chronic myeloid leukemia (CML), a hematological malignancy, is characterized by the Philadelphia chromosome, a chromosomal abnormality resulting from a translocation between chromosomes 9 and 22. Autophagy has emerged as a key factor in CML pathogenesis, promoting cancer cell survival and contributing to resistance against tyrosine kinase inhibitors (TKIs), the primary treatment for CML. Targeting autophagic pathways is being actively explored as a therapeutic approach to overcome drug resistance and enhance cancer cell death. Recent research highlights the intricate interplay between autophagy and CML progression, underscoring its role in disease biology and treatment outcomes. This review aims to provide a comprehensive analysis of the molecular and cellular mechanisms underlying CML, with a focus on the therapeutic potential of targeting autophagy.
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http://dx.doi.org/10.3390/biom15020215 | DOI Listing |
Sci Transl Med
March 2025
Department of Molecular Medicine, Scripps Research Institute, La Jolla, CA 92037, USA.
Interstitial lung disease (ILD) consists of a group of immune-mediated disorders that can cause inflammation and progressive fibrosis of the lungs, representing an area of unmet medical need given the lack of disease-modifying therapies and toxicities associated with current treatment options. Tissue-specific splice variants (SVs) of human aminoacyl-tRNA synthetases (aaRSs) are catalytic nulls thought to confer regulatory functions. One example from human histidyl-tRNA synthetase (HARS), termed HARS because the splicing event resulted in a protein encompassing the WHEP-TRS domain of HARS (a structurally conserved domain found in multiple aaRSs), is enriched in human lung and up-regulated by inflammatory cytokines in lung and immune cells.
View Article and Find Full Text PDFAm J Clin Pathol
March 2025
Department of Pathology, Stanford University, Stanford, CA, United States.
Objectives: Recent studies show that blocking CD47-SIRPα interactions is a promising target in checkpoint inhibition for cancer immunotherapy. However, to date, the expression of CD47 is not well characterized in various hematolymphoid neoplasms.
Methods: This study evaluates CD47 expression in a wide range of hematolymphoid neoplasms using immunohistochemistry on 834 cases.
Br J Pharmacol
March 2025
German Center for Lung Research (DZL), Universities of Giessen and Marburg Lung Center (UGMLC), Philipps University Marburg, Marburg, Germany.
Background And Purpose: Myeloid-derived suppressor cells (MDSCs) play important roles in the pathogenesis of asthma. Recent studies demonstrate that their function can be modulated by different pharmacological approaches. In this study, we focussed on the effects of systemically administered prostaglandin EP receptor agonist L-902,688 and pegylated human Arginase-1 on MDSCs in a murine model of chronic asthma and asthma exacerbation.
View Article and Find Full Text PDFTransplant Cell Ther
March 2025
Hematology Department, Hospital Universitari i Politècnic La Fe, València, Spain; Hematology Research Group, Institut d'Investigació Sanitària La Fe, València, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto Carlos III, Madrid, Spain; Medicine Department, Universitat de València, Spain.
Background: Despite the high incidence of diarrhea in hematopoietic cell transplant (HCT) recipients, data on infectious enterocolitis with post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis remain limited.
Objectives: Evaluate the characteristics, incidence, risk factors, and impact on outcomes of infectious enterocolitis in patients with hematologic malignancies undergoing HCT from matched sibling, matched unrelated, and haploidentical donors using PTCy as GVHD prophylaxis.
Study Design: Retrospective analysis of infectious enterocolitis episodes in 399 patients undergoing HCT at a single institution.
Donor Lymphocyte Infusion (DLI) is a crucial therapeutic strategy for relapsed myeloid malignancies post-allogeneic hematopoietic cell transplantation (allo-HCT), leveraging the graft-versus-leukemia (GvL) effect to restore immune control. While highly effective in chronic myeloid leukemia (CML), its efficacy in acute myeloid leukemia (AML) remains limited, with underlying mechanisms not fully understood. Recent research by Maurer and colleagues utilized cutting-edge technologies to dissect immune-leukemia interactions within the bone marrow niche, identifying a cytotoxic CD8+ T cell population as a key mediator of the anti-leukemic response.
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