B细胞恶性肿瘤,包括80多种异质血癌,由于复杂的致癌信号,对预后构成重大挑战。新出现的证据强调了脂质代谢中断在这些恶性肿瘤发展中的关键作用。脂质种类的变化,如磷脂,胆固醇,鞘脂,和脂肪酸,广泛存在于B细胞恶性肿瘤中,导致不受控制的细胞增殖和存活。磷脂在通过组成型B细胞受体(BCR)信号传导导致B细胞活化和恶性转化的初始信号传导级联中起关键作用。胆固醇和鞘脂稳态失调支持脂筏完整性,对于传播致癌信号至关重要。鞘脂影响恶性B细胞干细胞,扩散,和生存,脂筏中的鞘糖脂调节BCR激活。此外,癌细胞增强脂肪酸相关的过程,以满足更高的代谢需求。在肥胖个体中,肥胖来源的脂质和脂肪细胞周围的脂肪因子重新连接恶性B细胞中的脂质代谢,逃避细胞毒性疗法。遗传驱动因素如MYC易位也内在地改变恶性B细胞中的脂质代谢。总之,内在因素和外在因素融合以重新编程脂质代谢,在B细胞恶性肿瘤中培养侵袭性表型。因此,靶向改变的脂质代谢在改善不同B细胞恶性肿瘤亚型的风险分层和临床管理方面具有转化潜力.
B cell malignancies, comprising over 80 heterogeneous blood cancers, pose significant prognostic challenges due to intricate oncogenic signaling. Emerging evidence emphasizes the pivotal role of disrupted lipid metabolism in the development of these malignancies. Variations in lipid species, such as phospholipids, cholesterol, sphingolipids, and fatty acids, are widespread across B cell malignancies, contributing to uncontrolled cell proliferation and survival. Phospholipids play a crucial role in initial signaling cascades leading to B cell activation and malignant transformation through constitutive B cell receptor (BCR) signaling. Dysregulated cholesterol and sphingolipid homeostasis support lipid raft integrity, crucial for propagating oncogenic signals. Sphingolipids impact malignant B cell stemness, proliferation, and survival, while glycosphingolipids in lipid rafts modulate BCR activation. Additionally, cancer cells enhance fatty acid-related processes to meet heightened metabolic demands. In obese individuals, the obesity-derived lipids and adipokines surrounding adipocytes rewire lipid metabolism in malignant B cells, evading cytotoxic therapies. Genetic drivers such as MYC translocations also intrinsically alter lipid metabolism in malignant B cells. In summary, intrinsic and extrinsic factors converge to reprogram lipid metabolism, fostering aggressive phenotypes in B cell malignancies. Therefore, targeting altered lipid metabolism has translational potential for improving risk stratification and clinical management of diverse B cell malignancy subtypes.