Effect of D-mannose on Philadelphia chromosome-positive leukemia cells

Article type: Research Article

Authors: Okabe, Seiichi^* | Tanaka, Yuko | Gotoh, Akihiko

Affiliations: Department of Hematology, Tokyo Medical University, Tokyo, Japan

Correspondence: [*] Corresponding author: Seiichi Okabe, Department of Hematology, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. Tel.: +81 3 3342 6111; Fax: +81 3 5381 6651; E-mail: okabe@tokyo-med.ac.jp.

Abstract: 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: 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: We investigated whether D-mannose treatment induced metabolic changes in CML cells and reduced CML growth in the presence of ABL TKIs. 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: Our results indicate that metabolic reprogramming may be a useful strategy against Ph-positive leukemia cells. However, caution should be exercised during clinical applications.

Keywords: Chronic myeloid leukemia, D-mannose, glycolysis, ABL tyrosine kinase inhibitor

DOI: 10.3233/CBM-210141

Journal: Cancer Biomarkers, vol. 34, no. 3, pp. 337-346, 2022