Cancer Biomark. 2022;34(3):337-346. doi: 10.3233/CBM-210141.
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.
尽管 Abelson（ABL）酪氨酸激酶抑制剂（TKI）已被证明对慢性髓系白血病（CML）具有疗效，但在停止治疗后，CML 患者可能会对 ABL TKI 产生耐药性。
葡萄糖代谢可能会在 CML 细胞中发生改变，因为葡萄糖是肿瘤细胞使用的关键代谢物。我们研究了 D-甘露糖治疗是否会在 ABL TKI 存在的情况下诱导 CML 细胞发生代谢变化并减少 CML 生长。
我们研究了 D-甘露糖治疗是否会在 ABL TKI 存在的情况下诱导 CML 细胞发生代谢变化并减少 CML 生长。
D-甘露糖处理 72 h 可抑制 K562 细胞的生长。与对照细胞相比，ABL TKI 和 D-甘露糖联合治疗可诱导费城染色体（Ph）阳性白血病细胞产生更高水平的细胞毒性。在小鼠模型中，联合使用 ponatinib 和 D-甘露糖治疗组观察到严重的毒性，表现为体重减轻。
我们的结果表明，代谢重编程可能是对抗 Ph 阳性白血病细胞的一种有效策略。然而，在临床应用中应谨慎行事。
