Fabp4 is Essential for the Maintenance of Leukemia Stem Cells while Sparing Hematopoietic Stem Cells [bulkRNA-seq]. Fabp4 is Essential for the Maintenance of Leukemia Stem Cells while Sparing Hematopoietic Stem Cells [bulkRNA-seq]

Fatty acid-binding protein 4 (FABP4) plays a crucial role in the uptake, transport, and metabolic regulation of fatty acids. Previous research has found that the abnormal expression of FABP4 is associated with certain cancers, and it may become a new target for tumor therapy. We discovered that a haploinsufficient or absent dosage of Fabp4 does not affect the function of hematopoietic stem cells in mice, but significantly impacts the maintenance of leukemia stem cells (LSC). Our findings indicate that while Fabp4 does not influence the initiation of acute myeloid leukemia (AML) transformed by MLL-AF9 (MA9) in mice, it markedly promotes the progression of AML. A haploinsufficient or absent dosage of Fabp4 significantly extends the survival time of MA9 mice. Our research reveals the key role and mechanism of Fabp4 in MA9-LSC, suggesting that Fabp4 is a potential target for selectively eliminating MLL-rearranged leukemia. Overall design: Nine murine bone marrow samples,bone marrow cells from 3 wild-type, 3 heterozygous knockout, and 3 homozygous knockout mice for Fabp4.Nine vitro bone marrow samples,bone marrow cells from 3 wild-type, 3 heterozygous knockout, and 3 homozygous knockout mice for Fabp4

脂肪酸结合蛋白4（Fatty acid-binding protein 4, FABP4）在脂肪酸的摄取、转运及代谢调控中发挥关键作用。既往研究表明，FABP4的异常表达与部分癌症密切相关，有望成为肿瘤治疗的新型靶点。本研究发现，Fabp4单倍剂量不足或完全缺失不会影响小鼠造血干细胞的功能，但可显著影响白血病干细胞（Leukemia stem cells, LSC）的维持。研究结果显示，尽管Fabp4不会影响MLL-AF9（MA9）融合基因转化的急性髓系白血病（Acute myeloid leukemia, AML）在小鼠体内的起始过程，但可显著促进AML的疾病进展。Fabp4单倍剂量不足或完全缺失可显著延长MA9模型小鼠的生存时长。本研究揭示了Fabp4在MA9相关白血病干细胞中的核心作用与调控机制，提示Fabp4可作为选择性清除MLL重排型白血病的潜在治疗靶点。整体实验设计：9份小鼠骨髓样本，分别取自3只Fabp4野生型、3只Fabp4杂合敲除型及3只Fabp4纯合敲除型小鼠；另有9份体外骨髓样本，样本来源与上述一致。