Department of Pediatrics-Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Institute of Molecular Medicine, McGovern Medical School at the University of Texas Health Science Center (UT Health), Houston, Texas, USA.
Cancer Med. 2024 Jan;13(2):e6949. doi: 10.1002/cam4.6949.
Acute myeloid leukemia (AML) with an internal tandem duplication in the fms-like tyrosine kinase receptor 3 gene (FLT3-ITD) is associated with poor survival, and few studies have examined the impact of modifiable behaviors, such as nutrient quality and timing, in this subset of acute leukemia.
The influence of diet composition (low-sucrose and/or low-fat diets) and timing of diet were tested in tandem with anthracycline treatment in orthotopic xenograft mouse models. A pilot clinical study to test receptivity of pediatric leukemia patients to macronutrient matched foods was conducted. A role for the circadian protein, BMAL1 (brain and muscle ARNT-like 1), in effects of diet timing was studied by overexpression in FLT3-ITD-bearing AML cells.
Reduced tumor burden in FLT3-ITD AML-bearing mice was observed with interventions utilizing low-sucrose and/or low-fat diets, or time-restricted feeding (TRF) compared to mice fed normal chow ad libitum. In a tasting study, macronutrient matched low-sucrose and low-fat meals were offered to pediatric acute leukemia patients who largely reported liking the meals. Expression of the circadian protein, BMAL1, was heightened with TRF and the low-sucrose diet. BMAL1 overexpression and treatment with a pharmacological inducer of BMAL1 was cytotoxic to FLT3-ITD AML cells.
Mouse models for FLT3-ITD AML show that diet composition and timing slows progression of FLT3-ITD AML growth in vivo, potentially mediated by BMAL1. These interventions to enhance therapy efficacy show preliminary feasibility, as pediatric leukemia patients responded favorable to preparation of macronutrient matched meals.
具有 fms 样酪氨酸激酶受体 3 基因内部串联重复（FLT3-ITD）的急性髓系白血病（AML）与生存不良相关，很少有研究探讨可改变的行为，如营养质量和时间，对这组急性白血病的影响。
在同源移植小鼠模型中，与蒽环类药物治疗一起测试饮食成分（低糖和/或低脂肪饮食）和饮食时间的影响。进行了一项初步的临床研究，以测试儿科白血病患者对宏量营养素匹配食物的接受程度。通过在携带 FLT3-ITD 的 AML 细胞中过表达，研究了生物钟蛋白 BMAL1（脑和肌肉 ARNT 样 1）在饮食时间作用中的作用。
与自由进食的正常饲料相比，使用低糖和/或低脂肪饮食或限时喂养（TRF）的干预措施可观察到携带 FLT3-ITD 的 AML 小鼠肿瘤负担减少。在味觉研究中，向儿科急性白血病患者提供宏量营养素匹配的低糖和低脂肪餐，他们大多报告喜欢这些餐。TRF 和低糖饮食可提高生物钟蛋白 BMAL1 的表达。BMAL1 的过表达和 BMAL1 的药理学诱导剂的治疗对携带 FLT3-ITD 的 AML 细胞具有细胞毒性。
FLT3-ITD AML 的小鼠模型表明，饮食成分和时间可减缓体内 FLT3-ITD AML 生长的进展，这可能是通过 BMAL1 介导的。这些增强治疗效果的干预措施显示出初步的可行性，因为儿科白血病患者对宏量营养素匹配膳食的制备反应良好。
