CAMKIIδ Reinforces Lipid Metabolism and Promotes the Development of B Cell Lymphoma

• DOI: 10.1002/advs.202409513
• Publication Date: 2025-01-22T10:02:07Z
• Authors: Jiawei Zhang; Senlin Xu; Hui Fang; Dehao Wu; Ching Ouyang; Yunfei Shi; Zhenkang Hu; Mingfeng Zhang; Yaoyao Zhong; Junwei Zhao; Yichao Gan; Shize Zhang; Xiaoqian Liu; Jie Yin; Yuan Li; Mengyue Tang; Yingda Wang; Ling Li; Wing C Chan; David Horne; Mingye Feng; Wendong Huang; Ying Gu
• Keywords: CAMKIIδ; Science; lipid metabolism; Q; FOXO3A; B cell lymphoma

The most prevalent types of lymphomas are B cell (BCL). Newer therapies for BCL have improved the prognosis many patients. However, approximately 30% with aggressive either remain refractory or ultimately relapse. These patients urgently need other options. This study shows how calcium/calmodulin-dependent protein kinase II delta (CAMKIIδ) is pivotal development. In cells, ablation CAMKIIδ inhibits both lipolysis from lipid droplets and oxidative phosphorylation (OXPHOS). With blocked, progression markedly suppressed in two distinct mouse models: MYC-driven EµMyc mice Myc/Bcl2 double-expressed mice. When present, it destabilizes transcription factor Forkhead Box O3A (FOXO3A) by phosphorylating at Ser7 Ser12. then permits downstream gene IRF4 - a master metabolism. CAMKIIδ/FOXO3A axis bolsters metabolism, mitochondrial respiration, tumor fitness under metabolic stress. also evaluates Tetrandrine (TET), small molecule compound, as potent inhibitor. TET attenuates elicits therapeutic responses vitro vivo. Collectively, this highlights critical progression. results pave way innovative strategies treating BCL.