Acute myeloid leukemia (AML) is a hematological malignancy that commonly occurs in children. The prognosis of pediatric AML is relatively poor, thus threatening the patient's survival. The aberrant expression of the axon guidance factor, netrin-1, is observed in various types of malignancies, and it participates in the proliferation and apoptosis of tumor cells. Herein, we aimed to explore the role of netrin-1 in AML cells. Netrin-1 is highly expressed in AML patients. Proliferation and anti-apoptosis were observed in AML cells treated with netrin-1. The interaction between netrin-1 and Unc-5 netrin receptor B (UNC5B) was detected through coimmunoprecipitation, and UNC5B ribonucleic acid interference restrained the influence of netrin-1 on the AML cells. The phosphorylation of focal adhesion kinase-protein kinase B (FAK-Akt) was upregulated in AML cells treated with netrin-1. Both FAK and Akt inhibitors abrogated the effects of netrin-1 on the proliferation and apoptosis of AML cells. In conclusion, netrin-1 could promote the growth and reduce the apoptosis of AML cells in a concentration-dependent manner, and that these effects were mediated by activating the FAK-Akt signaling pathway via the UNC5B.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10088980 | PMC |
| http://dx.doi.org/10.1080/15384047.2023.2200705 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
O-GlcNAcylated FTO promotes m6A modification of SOX4 to enhance MDS/AML cell proliferation.
Cell Commun Signal
January 2025
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest University, Xi'an, P. R. China.
Fat mass and obesity-associated protein (FTO) was the first m6A demethylase identified, which is responsible for eliminating m6A modifications in target RNAs. While it is well-established that numerous cytosolic and nuclear proteins undergo O-GlcNAcylation, the possibility of FTO being O-GlcNAcylated and its functional implications remain unclear. This study found that a negative correlation between FTO expression and O-GlcNAcylation in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).
View Article and Find Full Text PDFBenzene-induced hematotoxicity enhances the self-renewal ability of HSPCs in Mll-Af9 mice.
Toxicology
January 2025
Key Laboratory of Chemical Safety and Health, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China; China State Key Laboratory of Trauma, Burn and Combined Injury, China. Electronic address:
Patients with benzene-induced leukemia undergo a continuous transformation from myelosuppression to malignant proliferation. However, the underlying mechanisms in this process remain unknown. Our previous studies have shown that the pathways involved in self-renewal capacity of bone marrow (BM) cells in Mll-Af9 mice exposed to benzene for life are significantly activated after severe blood toxicity.
View Article and Find Full Text PDFSingle-cell DNA sequencing reveals pervasive positive selection throughout preleukemic evolution.
Cell Genom
January 2025
Early Cancer Institute, University of Cambridge, Cambridge, UK. Electronic address:
The representation of driver mutations in preleukemic hematopoietic stem cells (pHSCs) provides a window into the somatic evolution that precedes acute myeloid leukemia (AML). Here, we isolate pHSCs from the bone marrow of 16 patients diagnosed with AML and perform single-cell DNA sequencing on thousands of cells to reconstruct phylogenetic trees of the major driver clones in each patient. We develop a computational framework that can infer levels of positive selection operating during preleukemic evolution from the statistical properties of these phylogenetic trees.
View Article and Find Full Text PDFGATA2 links stemness to chemotherapy resistance in acute myeloid leukemia.
Blood
January 2025
Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States.
Stemness-associated cell states are linked to chemotherapy resistance in AML. We uncovered a direct mechanistic link between expression of the stem cell transcription factor GATA2 and drug resistance. The GATA-binding protein 2 (GATA2) plays a central role in blood stem cell generation and maintenance.
View Article and Find Full Text PDFBispecific Aptamer-Drug Conjugates Selectively Eliminate Malignant Hematologic Cells for Treating Acute Myeloid Leukemia.
Langmuir
January 2025
Zhejiang Cancer Hospital, The Key Laboratory of Zhejiang Province for Nucleic Acids, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China.
Surface antigen-directed immunotherapy is a curative treatment modality for acute myeloid leukemia (AML) that is characterized by the abundance and stability expression of surface antigens. However, current surface antigen-directed immunotherapies have shown poor outcomes and undesirable mortality rates in treating AML patients, primarily due to acquired resistance that arises from using single-target therapies to address the heterogeneous expression of surface antigens. Hence, in order to improve the efficacy of antigen-specific therapies for treating AML, we designed a bispecific aptamer-drug conjugate.
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!