Effective Prevention and Treatment of Acute Leukemias in Mice by Activation of Thermogenic Adipose Tissues.
Ruibo ChenTianran ChengSisi XieXiaoting SunMingjia ChenShumin ZhaoQingyan RuanXiaolei NiMei RaoXinyi QuanKaiwen ChenShiyue ZhangTao ChengYuanfu XuYuguo ChenYunlong YangYihai CaoPublished in: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2024)
Acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) are common hematological malignancies in adults. Despite considerable research advances, the development of standard therapies, supportive care, and prognosis for the majority of AML and ALL patients remains poor and the development of new effective therapy is urgently needed. Here, it is reported that activation of thermogenic adipose tissues (TATs) by cold exposure or β3-adrenergic receptor agonists markedly alleviated the development and progression of AML and ALL in mouse leukemia models. TAT activation (TATA) monotherapy substantially reduces leukemic cells in bone marrow and peripheral blood, and suppresses leukemic cell invasion, including hepatomegaly and splenomegaly. Notably, TATA therapy prolongs the survivals of AML- and ALL-bearing mice. Surgical removal of thermogenic brown adipose tissue (BAT) or genetic deletion of uncoupling protein 1 (UCP1) largely abolishes the TATA-mediated anti-leukemia effects. Metabolomic pathway analysis demonstrates that glycolytic metabolism, which is essential for anabolic leukemic cell growth, is severely impaired in TATA-treated leukemic cells. Moreover, a combination of TATA therapy with chemotherapy produces enhanced anti-leukemic effects and reduces chemotoxicity. These data provide a new TATA-based therapeutic paradigm for the effective treatment of AML, ALL, and likely other types of hematological malignancies.
Keyphrases
- acute myeloid leukemia
- allogeneic hematopoietic stem cell transplantation
- adipose tissue
- induced apoptosis
- acute lymphoblastic leukemia
- bone marrow
- peripheral blood
- insulin resistance
- cell cycle arrest
- newly diagnosed
- signaling pathway
- combination therapy
- gene expression
- end stage renal disease
- ejection fraction
- healthcare
- mesenchymal stem cells
- endoplasmic reticulum stress
- high fat diet induced
- liver failure
- squamous cell carcinoma
- type diabetes
- metabolic syndrome
- stem cells
- high fat diet
- machine learning
- intensive care unit
- peritoneal dialysis
- clinical trial
- electronic health record
- cell therapy
- randomized controlled trial
- chronic pain
- open label
- cell death
- quality improvement
- deep learning
- locally advanced
- hepatitis b virus
- wild type
- small molecule
- pain management
- artificial intelligence
- binding protein
- nitric oxide synthase
- acute respiratory distress syndrome