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

Autor: Ruibo Chen, Tianran Cheng, Sisi Xie, Xiaoting Sun, Mingjia Chen, Shumin Zhao, Qingyan Ruan, Xiaolei Ni, Mei Rao, Xinyi Quan, Kaiwen Chen, Shiyue Zhang, Tao Cheng, Yuanfu Xu, Yuguo Chen, Yunlong Yang, Yihai Cao
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Advanced Science, Vol 11, Iss 38, Pp n/a-n/a (2024)
Druh dokumentu: article
ISSN: 2198-3844
48089281
DOI: 10.1002/advs.202402332
Popis: 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.
Databáze: Directory of Open Access Journals
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