Background: A major issue in Chronic Myeloid Leukemia (CML) is the persistence of quiescent leukemia stem cells (LSCs) in the hematopoietic niche under tyrosine kinase inhibitor (TKI) treatment.
Results: Here, using CFSE sorting, we show that low-proliferating CD34+ cells from CML patients in 3D co-culture hide under HS27A stromal cells during TKI treatment-a behavior less observed in untreated cells. Under the same conditions, Ba/F3p210 cells lose their spontaneous motility. In CML CD34+ and Ba/F3p210 cells, while Rac1 is completely inhibited by TKI, RhoA remains activated but is unable to signal to ROCK. Co-incubation of Ba/F3p210 cells with TKI, SKF-96365 (a calcium channel inhibitor), and EGF restores myosin II activation and amoeboid motility to levels comparable to untreated cells, sustaining the activation of ROCK. In CFSE+ CD34+ cells containing quiescent leukemic stem cells, co-incubation of TKI with SKF-96365 induced the expulsion of these cells from the HS27A niche.
Conclusions: This study underscores the role of RhoA in LSC behavior under TKI treatment and suggests that SKF-96365 could remobilize quiescent CML LSCs through reactivation of the RhoA/ROCK pathway.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11352811 | PMC |
| http://dx.doi.org/10.3390/cancers16162791 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
B-Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma Mimicking Fibrosing Mediastinitis: A Case Report and Diagnostic Insight.
Am J Case Rep
December 2024
Division of Respirology, Rheumatology, Infectious Diseases, and Neurology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki, Japan.
BACKGROUND Fibrosing mediastinitis (FM) is a rare, fibroproliferative disorder within the mediastinum. It is extremely rare for hematologic malignancies to develop as FM. CASE REPORT A 32-year-old Japanese man with a 1-month history of headache and 2-week history of facial swelling underwent chest computed tomography (CT); a diffuse mass-like lesion was revealed in the anterior mediastinum with severe stenosis of vital mediastinal organs.
View Article and Find Full Text PDFEffect of dietary supplementation of jujube fruit (Ziziphus jujuba) powder on performance, some biochemical parameters, and egg quality in quails (Coturnix coturnix japonica).
Pol J Vet Sci
June 2024
Elazıg Veterinary Control Institute, Republic of Turkey Ministry of Agriculture and Forestry, 23200, Elazig, Turkey.
This study aimed to evaluate the effects of different dietary supplementation levels with jujube fruit powder on the performance, biochemical parameters, and egg quality characteristics of laying quails. A total of 60 quails (45 days old) were randomly assigned to treatments with different levels of jujube fruit powder: a basal diet (control) and diets supplemented with 5 g/kg (T1), 10 g/kg (T2), with five replicates per treatment (20 quails/treatment and four quails/replicate). The differences between 1-15 and 16-30 days for feed intake (p<0.
View Article and Find Full Text PDFEffect of repeated semen ejaculation on sperm quality and selected biochemical markers of canine semen.
Pol J Vet Sci
June 2024
Department of Animal Biochemistry and Biotechnology, University of Warmia and Mazury in Olsztyn, Oczapowskiego 5, 10-718 Olsztyn-Kortowo, Poland.
The aim of this study was to evaluate the quality parameters and selected biochemical markers of canine semen sampled at 24-h intervals over a period of 5 days, preceded by 6 months of sexual abstinence. Full ejaculates were obtained from 6 dogs. Ejaculate volume and total sperm counts in the ejaculate decreased gradually on successive sampling days.
View Article and Find Full Text PDFThe effect of silymarin on diabetes mellitus-induced male rats reproductive impairment: Evidences for role of heat shock proteins 70 and 90.
Pol J Vet Sci
December 2024
Department of Basic sciences, Faculty of Veterinary Medicine, Tabriz medical sciences branch, Islamic Azad University, 5159115705, Tabriz, Iran.
Male fertility is adversely influenced by diabetes. The beneficial effects of antioxidant bioflavonoids in improving fertility have been reported. This study was conducted to evaluate the effects of silymarin on diabetes mellitus-induced male reproductive impairment in rats by investigating its role in Hsp70 and Hsp90 expression.
View Article and Find Full Text PDFCellular distribution of some intermediate filaments in the rat mammary gland during pregnancy, lactation and involution.
Pol J Vet Sci
December 2024
Department of Histology and Embryology, Faculty of Veterinary Medicine, University of Dicle, 21280 Diyarbakır, Turkey.
Intermediate filaments (IFs) play a major role in determining and maintaining cell shape and anchoring intracellular organelles in place, in the tissues and organs of several species, starting from the early stages of development. This study was aimed at the immunohistochemical investigation of the presence, cellular localization and temporal distribution of the intermediate filaments keratin 8 (CK8), keratin 18 (CK18), keratin 19 (CK19), vimentin, desmin and laminin, all of which contribute to the formation of the cytoskeleton in the rat mammary gland during pregnancy, lactation and involution. On days 7, 14 and 21 of pregnancy (pregnancy period), on day 7 post-delivery (lactation period) and on day 7 post-weaning (involution period), under ketamine hydrochloride (Ketalar-Pfizer) (90 mg/kg) anesthesia, two mammary glands were fully excised from the abdominal region.
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!