Acute myeloid leukemia (AML) is a heterogeneous hematopoietic disorder with a poor prognosis. The clinical significance of Leukemia stem cells (LSCs) plays an important role in the generation of AML and is the main cause of the recurrence after remission. Osteopontin (OPN), an extracellular matrix protein, has been implicated in hematopoietic malignancies. However, the specific role and the underlying mechanism of AML cell autocrined OPN in leukemia maintenance remain unknown. Here, we showed that knockdown of Opn expression significantly prolonged the survival of mice with MLL-AF9 cell-induced AML and markedly reduced the tumor burden. The LSCs from the Opn-knockdown groups exhibited decreased numbers and impaired function as determined by immunophenotype, colony-forming and limiting dilution assays. Further analysis revealed that Opn prevents LSCs from undergoing apoptosis and cell cycle arrest. Repression of OPN in human AML cell lines in vitro mimics the phenotypes observed in the mouse model. Overall, our data indicated that OPN is a potent therapeutic target for eradicating LSCs in AML.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bbrc.2022.02.022 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Tyrosine Kinase Inhibitor Treatment Patterns in Patients With Chronic-Phase Chronic Myeloid Leukemia: A Single Center Data From China.
Clin Lymphoma Myeloma Leuk
December 2024
Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; Hematology Center, Peking University People's Hospital, Qingdao, China. Electronic address:
Aim: To describe tyrosine kinase inhibitor (TKI) treatment patterns and analyze co-variates of TKI switch for chronic myeloid leukemia (CML) patients in a center from China.
Methods: A retrospectively study was designed to analyze TKI switching patterns, reasons and associated covariates in patients with CP-CML.
Results: 1766 patients receiving initial imatinib (n = 1374), nilotinib (n = 254), dasatinib (n = 63) and flumatinib (n = 75) therapy were retrospectively interrogated.
Construction of a stromal-related prognostic model in acute myeloid leukemia by comprehensive bioinformatics analysis.
Curr Res Transl Med
January 2025
Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:
Background: Stromal cells play a pivotal role in the tumor microenvironment (TME), significantly impacting the progression of acute myeloid leukemia (AML). This study sought to develop a stromal-related prognostic model for AML, aiming to uncover novel prognostic markers and therapeutic targets.
Methods: RNA expression data and clinical profiles of AML patients were retrieved from the Cancer Genome Atlas (TCGA).
Cellular automata modelling of leukaemic stem cell dynamics in acute myeloid leukaemia: insights into predictive outcomes and targeted therapies.
R Soc Open Sci
January 2025
Department of Anatomy, Kanazawa Medical University, Uchinada, Ishikawa 9200293, Japan.
Acute myeloid leukaemia (AML) is a haematologic malignancy with high relapse rates in both adults and children. Leukaemic stem cells (LSCs) are central to leukaemopoiesis, treatment response and relapse and frequently associated with measurable residual disease (MRD). However, the dynamics of LSCs within the AML microenvironment is not fully understood.
View Article and Find Full Text PDFIsolated Central Nervous System Infiltrated and Progressed to Acute Myeloid Leukemia from Chronic Myeloid Leukemia with e1a3 BCR-ABL1 Transcript: A Rare Case Report and Literature Review.
Cancer Manag Res
January 2025
Medical Center of Hematology, Xinqiao Hospital, Army Medical University, Chongqing, People's Republic of China.
The chronic myeloid leukemia (CML) is easily diagnosed by laboratory examination, however, rare BCR-ABL1 mRNA transcripts variants, such as e1a3 present diagnosis and therapeutic challenges. This case report details the diagnosis and management of a CML patient with the e1a3 transcript by FISH and RT-PCR. Following initial diagnosis, the patient was treated with the tyrosine kinase inhibitor (TKI) Flumatinib.
View Article and Find Full Text PDFA 31-year-old male with a plasmacytoid dendritic blast cell neoplasm.
Ecancermedicalscience
November 2024
Internal Medicine Service, Sanatorio Sagrado Corazón, Buenos Aires, CP 1039, Argentina.
Plasmacytoid blast dendritic cell neoplasm is a rare subtype of acute leukaemia that represents less than 1% of haematologic neoplasms. It is characterised by skin involvement and leukaemic dissemination in the rest of the body. The immunophenotype is represented by the expression of CD4, CD56 and CD123.
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!