Fabp4 is Essential for the Maintenance of Leukemia Stem Cells while Sparing Hematopoietic Stem Cells

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: Three murine bone marrow samples, each a mixture of bone marrow cells from two wild-type, two heterozygous knockout, and two homozygous knockout mice for Fabp4.