Effects of Weicanqing Formula （微残清方） on Malic Enzyme 2-Mediated Bone Marrow Immunemetabolic Homeostasis in Acute Myeloid Leukemia Model Mice
10.13288/j.11-2166/r.2026.12.012
- VernacularTitle:微残清方对急性髓系白血病模型小鼠骨髓苹果酸酶2介导的骨髓免疫代谢平衡的影响
- Author:
Chenyang FAN
1
;
Lixiang YAN
1
;
Xiaogang HAO
1
;
Xinli ZHOU
1
;
Reaila JIANATI
1
;
Yifei GUO
1
;
Gengda ZHU
1
;
Zhexin SHI
1
Author Information
1. First Teaching Hospital of Tianjin University of Traditional Chinese Medicine/ National Clinical Research Center for Chinese Medicine，Tianjin，300380
- Publication Type:Journal Article
- Keywords:
acute myeloid leukemia;
immunometabolic homeostasis;
malic enzyme 2;
bone marrow T-cell subpopulations;
Weicanqing Formula （微残清方）
- From:
Journal of Traditional Chinese Medicine
2026;67(12):1315-1322
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the potential mechanism of Weicanqing Formula （微残清方， WF） combined with chemotherapy in treating acute myeloid leukemia （AML） based on malic enzyme 2 （ME2）-mediated bone marrow immune-metabolic homeostasis and . MethodsSixty-five male C57BL/6N mice were randomly divided into control group， model group， WF group， chemotherapy group， and the combination group （WF plus chemotherapy）， with 13 mice per group. Except for the control group， mice were injected with C1498 cells （appro-ximately 1×106 cells per mouse） via the tail vein on day 1 to establish an AML model. Starting from day 8， mice in the chemotherapy group and the combination group were administered with cytarabine at 30 mg/（kg·d） via subcutaneous injection， once daily for 3 consecutive days； WF group and the combination group received WF at 7.54 g/（kg·d） by gavage， once daily for 21 consecutive days. On days 1， 7， 14， 21 and 28， hemoglobin （Hb） and white blood cell （WBC） levels were determined in each group. On day 28， Giemsa staining was used to observe morphological changes in bone marrow cells. Flow cytometry was employed to detect the expression levels of bone marrow T lympthocyte subsets， including CD8+， CD4+， and regulatory T lymphocytes （Treg）. The contents of glutamine （Gln）， nicotinamide adenine dinucleotide phosphate （NADP⁺）， and reduced nicotinamide adenine dinucleotide phosphate （NADPH） in bone marrow were determined using visible spectrophotometry. Adenosine triphosphate （ATP） concentration in bone marrow was measured by chemiluminescence assay. The mRNA expression of malic enzyme 2 （ME2） in bone marrow was detected by RT-qPCR， and the protein expression level of ME2 was determined by Western blotting. ResultsCompared to the control group， the model group showed decreased Hb levels on day 14， 21， and 28， and increased WBC levels on day 7， 14， 21， and 28 （P＜0.05）. On day 28， bone marrow CD8+ and CD8+/CD4+ levels decreased， while Treg cells， ATP， Gln， NADP+， NADPH， ME2 mRNA， and their corresponding protein levels increased （P＜0.05）. Compared to the model group， the chemotherapy group and the combination group both exhibited reduced Hb level on day 14， 21 and 28， as well as the increased WBC level； the combination group showed increased CD8+ level， decreased Treg， ATP， Gln， and NADPH content， as well as reduced ME2 mRNA expression and protein levels （P＜0.05）. Compared to the chemotherapy group， the combination group showed significantly increased Hb level on days 21 and 28， and increased WBC level on day 28 （P＜0.05）. Bone marrow smear pathology revealed that， in the model group， myeloid blast cells exhibited cytoplasmic vacuoles indicative of abnormal metabolic activity. In contrast， both the chemotherapy group and the combination group showed large numbers of metamyelocytes and band neutrophils， with only a few immature granulocytic blast cells observed. ConclusionWF may improve the prognosis of AML when used as an adjunct to chemotherapy by modulating ME2 expression， inhibiting metabolic energy competition within the bone marrow microenvironment， and reshaping the distribution of T lymphocyte subsets in the bone marrow.
