biostudies-literatureYe HNHLBI NIH HHSNCI NIH HHSNIHNIGMS NIH HHS500-519https://www.ebi.ac.uk/biostudies/studies/S-EPMC7858222biostudies-literatureUnknown11(2)Due to the disseminated nature of leukemia, malignant cells are exposed to many different tissue microenvironments, including a variety of extramedullary sites. In the present study, we demonstrate that leukemic cells residing in the liver display unique biological properties and also contribute to systemic changes that influence physiologic responses to chemotherapy. Specifically, the liver microenvironment induces metabolic adaptations via upregulating expression of endothelial lipase in leukemia cells, which not only stimulates tumor cell proliferation through polyunsaturated fatty acid-mediated pathways, but also promotes survival by stabilizing antiapoptotic proteins. Additionally, hepatic infiltration and tissue damage caused by malignant cells induces release of liver-derived enzymeCancer discoveryThe Hepatic Microenvironment Uniquely Protects Leukemia Cells through Induction of Growth and Survival Pathways Mediated by LIPG.PMC7858222T32 CA190216R01 CA220986P30 CA046934R01 CA166265P30CA046934RO1CA166265R01 HL146442T32 GM008497RO1CA220986R21 HL150032R01 HL149714R01 HL148151Krug AD'Alessandro ASchniedewind BAmaya MLPei SChou CHInguva AChristians UPollyea DAMinhajuddin MJordan CTGrimes HLDe Bloois ECulp-Hill RStevens BMPonder JYe HfalseThe Hepatic Microenvironment Uniquely Protects Leukemia Cells through Induction of Growth and Survival Pathways Mediated by LIPG.Due to the disseminated nature of leukemia, malignant cells are exposed to many different tissue microenvironments, including a variety of extramedullary sites. In the present study, we demonstrate that leukemic cells residing in the liver display unique biological properties and also contribute to systemic changes that influence physiologic responses to chemotherapy. Specifically, the liver microenvironment induces metabolic adaptations via upregulating expression of endothelial lipase in leukemia cells, which not only stimulates tumor cell proliferation through polyunsaturated fatty acid-mediated pathways, but also promotes survival by stabilizing antiapoptotic proteins. Additionally, hepatic infiltration and tissue damage caused by malignant cells induces release of liver-derived enzyme2021-01-01T00:00:00Z2021 Feb2025-04-21T23:42:35.224Z2022-02-11T00:45:47.21ZS-EPMC78582223302862110.1158/2159-8290.CD-20-031810.1158/2159-8290.cd-20-0318