Effect of D-mannose on Philadelphia chromosome-positive leukemia cells.
ABL tyrosine kinase inhibitor
Chronic myeloid leukemia
D-mannose
glycolysis
Journal
Cancer biomarkers : section A of Disease markers
ISSN: 1875-8592
Titre abrégé: Cancer Biomark
Pays: Netherlands
ID NLM: 101256509
Informations de publication
Date de publication:
2022
2022
Historique:
pubmed:
11
1
2022
medline:
25
5
2022
entrez:
10
1
2022
Statut:
ppublish
Résumé
Although Abelson (ABL) tyrosine kinase inhibitors (TKIs) have demonstrated potency against chronic myeloid leukemia (CML), resistance to ABL TKIs can develop in CML patients after discontinuation of therapy. Glucose metabolism may be altered in CML cells because glucose is a key metabolite used by tumor cells. We investigated whether D-mannose treatment induced metabolic changes in CML cells and reduced CML growth in the presence of ABL TKIs. We investigated whether D-mannose treatment induced metabolic changes in CML cells and reduced CML growth in the presence of ABL TKIs. Treatment with D-mannose for 72 h inhibited the growth of K562 cells. Combined treatment using ABL TKIs and D-mannose induced a significantly higher level of cytotoxicity in Philadelphia chromosome (Ph)-positive leukemia cells than in control cells. In the mouse model, severe toxicity was observed as evidenced by body weight loss in the ponatinib and D-mannose combination treatment groups. Our results indicate that metabolic reprogramming may be a useful strategy against Ph-positive leukemia cells. However, caution should be exercised during clinical applications.
Sections du résumé
BACKGROUND
BACKGROUND
Although Abelson (ABL) tyrosine kinase inhibitors (TKIs) have demonstrated potency against chronic myeloid leukemia (CML), resistance to ABL TKIs can develop in CML patients after discontinuation of therapy.
OBJECTIVE
OBJECTIVE
Glucose metabolism may be altered in CML cells because glucose is a key metabolite used by tumor cells. We investigated whether D-mannose treatment induced metabolic changes in CML cells and reduced CML growth in the presence of ABL TKIs.
METHODS
METHODS
We investigated whether D-mannose treatment induced metabolic changes in CML cells and reduced CML growth in the presence of ABL TKIs.
RESULTS
RESULTS
Treatment with D-mannose for 72 h inhibited the growth of K562 cells. Combined treatment using ABL TKIs and D-mannose induced a significantly higher level of cytotoxicity in Philadelphia chromosome (Ph)-positive leukemia cells than in control cells. In the mouse model, severe toxicity was observed as evidenced by body weight loss in the ponatinib and D-mannose combination treatment groups.
CONCLUSION
CONCLUSIONS
Our results indicate that metabolic reprogramming may be a useful strategy against Ph-positive leukemia cells. However, caution should be exercised during clinical applications.
Identifiants
pubmed: 35001876
pii: CBM210141
doi: 10.3233/CBM-210141
doi:
Substances chimiques
Protein Kinase Inhibitors
0
Mannose
PHA4727WTP
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM