American Association for Cancer Research
00085472can161645-sup-167765_1_supp_3813154_5jdn2t.docx (133.08 kB)

Supplementary Tables S1-S5 from Bone Marrow Adipocytes Facilitate Fatty Acid Oxidation Activating AMPK and a Transcriptional Network Supporting Survival of Acute Monocytic Leukemia Cells

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journal contribution
posted on 2023-03-31, 01:10 authored by Yoko Tabe, Shinichi Yamamoto, Kaori Saitoh, Kazumasa Sekihara, Norikazu Monma, Kazuho Ikeo, Kaoru Mogushi, Masato Shikami, Vivian Ruvolo, Jo Ishizawa, Numsen Hail, Saiko Kazuno, Mamoru Igarashi, Hiromichi Matsushita, Yasunari Yamanaka, Hajime Arai, Isao Nagaoka, Takashi Miida, Yoshihide Hayashizaki, Marina Konopleva, Michael Andreeff

Clinical characteristics of AMoL patients (S1); Quantitative expression of metabolites in U937 cells after BM-adipocyte co-culture and etomoxir treatment (S2); Genes whose expression was altered in U937 cells co-cultured with MSCs or BM-adipocytes and treated with etomoxir (S3); Genes whose expression was altered most often in U937 and THP1 cells by BM-adipocyte co-culture and treatment with etomoxir (S4); Proteins whose expression was altered in U937 cells by BM-adipocyte co-culture (S5).



National Health and Medical Research Council

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Paul and Mary Haas Chair in Genetics



Leukemia cells in the bone marrow must meet the biochemical demands of increased cell proliferation and also survive by continually adapting to fluctuations in nutrient and oxygen availability. Thus, targeting metabolic abnormalities in leukemia cells located in the bone marrow is a novel therapeutic approach. In this study, we investigated the metabolic role of bone marrow adipocytes in supporting the growth of leukemic blasts. Prevention of nutrient starvation–induced apoptosis of leukemic cells by bone marrow adipocytes, as well as the metabolic and molecular mechanisms involved in this process, was investigated using various analytic techniques. In acute monocytic leukemia (AMoL) cells, the prevention of spontaneous apoptosis by bone marrow adipocytes was associated with an increase in fatty acid β-oxidation (FAO) along with the upregulation of PPARγ, FABP4, CD36, and BCL2 genes. In AMoL cells, bone marrow adipocyte coculture increased adiponectin receptor gene expression and its downstream target stress response kinase AMPK, p38 MAPK with autophagy activation, and upregulated antiapoptotic chaperone HSPs. Inhibition of FAO disrupted metabolic homeostasis, increased reactive oxygen species production, and induced the integrated stress response mediator ATF4 and apoptosis in AMoL cells cocultured with bone marrow adipocytes. Our results suggest that bone marrow adipocytes support AMoL cell survival by regulating their metabolic energy balance and that the disruption of FAO in bone marrow adipocytes may be an alternative, novel therapeutic strategy for AMoL therapy. Cancer Res; 77(6); 1453–64. ©2017 AACR.