Persistence of drug-resistant quiescent leukemic stem cells (LSC) and impaired natural killer (NK) cell immune response account for relapse of chronic myelogenous leukemia (CML). Inactivation of protein phosphatase 2A (PP2A) is essential for CML-quiescent LSC survival and NK cell antitumor activity. Here we show that has antiproliferative and PP2A-activating functions that are dose dependently differentially induced by CCND2/CDK6 and SET inhibition, respectively. is upregulated in CML LSCs and NK cells by bone marrow microenvironment (BMM) signals to induce quiescence and impair immune response, respectively. Conversely, BCR-ABL1 downregulates in CML progenitors to prevent growth arrest and PP2A-mediated apoptosis. Quiescent LSCs escape apoptosis by upregulating long noncoding RNA that uncouples and limits function to cytostasis. Genetic and pharmacologic modulation and/or PP2A-activating drug treatment restore NK cell activity, inhibit BMM-induced growth arrest, and selectively trigger LSC apoptosis and in patient-derived xenografts; hence, the importance of and PP2A activity for CML development and therapy.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510943 | PMC |
| http://dx.doi.org/10.1158/0008-5472.BCD-19-0039 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Diversification of -harbouring plasmids among carbapenemase-producing , 11 years after a large outbreak in a general hospital in the Netherlands.
Microb Genom
January 2025
Center for Infectious Disease Control (CIb), National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands.
Genes encoding OXA-48-like carbapenem-hydrolyzing enzymes are often located on plasmids and are abundant among carbapenemase-producing (CPE) worldwide. After a large plasmid-mediated outbreak in 2011, routine screening of patients at risk of CPE carriage on admission and every 7 days during hospitalization was implemented in a large hospital in the Netherlands. The objective of this study was to investigate the dynamics of the hospitals' 2011 outbreak-associated plasmid among CPE collected from 2011 to 2021.
View Article and Find Full Text PDFPersisting Gaps in Cytomegalovirus Prevention and Management After Solid Organ Transplantation in a Resource-Limited Setting.
Transpl Infect Dis
January 2025
Department of Infectious Diseases, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Brazil.
Background: Cytomegalovirus (CMV) infection remains among the leading complications after solid organ transplantation (SOT). Large international surveys mainly focused on high-income countries, detected considerable variability in the management of this infection after SOT. Limited data are available from resource-limited settings.
View Article and Find Full Text PDFAntipsychotic off-label use in the 21st century: An enduring public health concern.
Dialogues Clin Neurosci
December 2025
University Bordeaux, Inserm, Bordeaux Population Health Research Center, Team Pharmacoepidemiology, UMR 1219, Bordeaux, France.
Soon after the introduction of second-generation antipsychotics, antipsychotic off-label use (OLU) progressively became a common prescribing practice. This evolving practice should be regularly monitored considering the growing number of persons exposed to the adverse effects of antipsychotics. The aim of the present review was to synthesise the literature published over the last 15 years on antipsychotic OLU for mental health symptoms.
View Article and Find Full Text PDFMicrowave-synthesized NiZrO@GNP and NiZrO3@MWCNT nanocomposites: enhanced antimicrobial efficacy against biofilms and .
3 Biotech
February 2025
Catalysis and Nanomaterials Research Laboratory, Department of Chemistry, Loyola College, Chennai, Tamil Nadu 600034 India.
Unlabelled: The persistent challenge posed by antibiotic-resistant bacteria and tuberculosis necessitates innovative approaches to antimicrobial treatment. This study explores the synthesis and characterization of NiZrO₃ nanoparticles integrated with graphene nanoplatelets (GNP) and multi-walled carbon nanotubes (MWCNT), using a microwave-assisted green synthesis route, employing fenugreek () seed extract as a gelling agent. The synthesised nanocomposites were systematically analyzed using XRD, FT-IR, Raman spectroscopy, HR-SEM and HR TEM analysis to assess structural, optical, and morphological properties.
View Article and Find Full Text PDFEvolving Therapeutic Strategies in Esophageal Squamous Cell Carcinoma: Advances and Perspectives.
J Cancer Prev
December 2024
Department of Animal Science and Biotechnology, Research Institute for Innovative Animal Science, Kyungpook National University, Sangju, Korea.
Esophageal squamous cell carcinoma (ESCC) is among the most prevalent forms of esophageal cancer globally, with a particularly high incidence in developing countries. Notably, Asia accounts for approximately 80% of global esophageal cancer cases, with China alone contributing to 54% of this burden. The primary treatment modality for ESCC remains esophagectomy, primarily employed for locally advanced disease, often in combination with chemotherapy and radiotherapy for advanced-stage cases.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!