2. Academic Validation
  3. Effective Prevention and Treatment of Acute Leukemias in Mice by Activation of Thermogenic Adipose Tissues

Effective Prevention and Treatment of Acute Leukemias in Mice by Activation of Thermogenic Adipose Tissues

  • Adv Sci (Weinh). 2024 Jul 25:e2402332. doi: 10.1002/advs.202402332.
Ruibo Chen 1,  Tianran Cheng 2,  Sisi Xie 3,  Xiaoting Sun 4,  Mingjia Chen 1,  Shumin Zhao 3,  Qingyan Ruan 3,  Xiaolei Ni 3,  Mei Rao 3,  Xinyi Quan 1,  Kaiwen Chen 1,  Shiyue Zhang 2,  Tao Cheng 2,  Yuanfu Xu 2,  Yuguo Chen 5,  Yunlong Yang 1,  Yihai Cao 6
Affiliations

Affiliations

  • 1 Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
  • 2 State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China.
  • 3 Department of Cardiology, Basic Scientific Research Center, Longyan First Hospital Affiliated to Fujian Medical University, Longyan, 364000, China.
  • 4 Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, 325035, China.
  • 5 Department of Emergency Medicine, Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Medical and Pharmaceutical Basic Research Innovation Center of Emergency and Critical Care Medicine, China's Ministry of Education, NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, Shandong International Cooperative Laboratory for Emergency and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, 250012, China.
  • 6 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Solna, 17165, Sweden.
PMID: 39049685 DOI: 10.1002/advs.202402332
Abstract

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.

Keywords

cancer therapy; glycolysis; leukemia; metabolism; thermogenic adipose tissue.

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