REFERENCES
1. Hassan M, Abedi-Valugerdi M. Hematologic malignancies in elderly patients. Haematologica 2014;99:1124-7.
2. Jones RG, Thompson CB. Tumor suppressors and cell metabolism: a recipe for cancer growth. Genes Dev 2009;23:537-48.
4. Raaijmakers MH. Niche contributions to oncogenesis: emerging concepts and implications for the hematopoietic system. Haematologica 2011;96:1041-8.
5. Ho TC, LaMere M, Stevens BM, et al. Evolution of acute myelogenous leukemia stem cell properties after treatment and progression. Blood 2016;128:1671-8.
6. Robinson AJ, Davies S, Darley RL, Tonks A. Reactive oxygen species rewires metabolic activity in acute myeloid leukemia. Front Oncol 2021;11:632623.
7. Romo-González M, Ijurko C, Hernández-Hernández Á. Reactive oxygen species and metabolism in leukemia: a dangerous liaison. Front Immunol 2022;13:889875.
8. Tabe Y, Konopleva M. Advances in understanding the leukaemia microenvironment. Br J Haematol 2014;164:767-78.
9. Zhao Y, Butler EB, Tan M. Targeting cellular metabolism to improve cancer therapeutics. Cell Death Dis 2013;4:e532.
10. Molina JR, Sun Y, Protopopova M, et al. An inhibitor of oxidative phosphorylation exploits cancer vulnerability. Nat Med 2018;24:1036-46.
11. Hail N, Lotan R. Cancer chemoprevention and mitochondria: targeting apoptosis in transformed cells via the disruption of mitochondrial bioenergetics/redox state. Mol Nutr Food Res 2009;53:49-67.
12. Benito J, Shi Y, Szymanska B, et al. Pronounced hypoxia in models of murine and human leukemia: high efficacy of hypoxia-activated prodrug PR-104. PLoS One 2011;6:e23108.
13. Benito J, Zeng Z, Konopleva M, Wilson WR. Targeting hypoxia in the leukemia microenvironment. Int J Hematol Oncol 2013;2:279-88.
14. Rytelewski M, Harutyunyan K, Baran N, et al. Inhibition of oxidative phosphorylation reverses bone marrow hypoxia visualized in imageable syngeneic B-all mouse model. Front Oncol 2020;10:991.
15. Frolova O, Samudio I, Benito JM, et al. Regulation of HIF-1α signaling and chemoresistance in acute lymphocytic leukemia under hypoxic conditions of the bone marrow microenvironment. Cancer Biol Ther 2012;13:858-70.
16. Gut P, Verdin E. The nexus of chromatin regulation and intermediary metabolism. Nature 2013;502:489-98.
17. Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 1997;3:730-7.
18. Lapidot T, Sirard C, Vormoor J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 1994;367:645-8.
19. Viale A, Pettazzoni P, Lyssiotis CA, et al. Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function. Nature 2014;514:628-32.
20. Lee KM, Giltnane JM, Balko JM, et al. MYC and MCL1 cooperatively promote chemotherapy-resistant breast cancer stem cells via regulation of mitochondrial oxidative phosphorylation. Cell Metab 2017;26:633-47.e7.
21. Lagadinou ED, Sach A, Callahan K, et al. BCL-2 inhibition targets oxidative phosphorylation and selectively eradicates quiescent human leukemia stem cells. Cell Stem Cell 2013;12:329-41.
22. Eppert K, Takenaka K, Lechman ER, et al. Stem cell gene expression programs influence clinical outcome in human leukemia. Nat Med 2011;17:1086-93.
23. Jung N, Dai B, Gentles AJ, Majeti R, Feinberg AP. An LSC epigenetic signature is largely mutation independent and implicates the HOXA cluster in AML pathogenesis. Nat Commun 2015;6:8489.
24. George J, Uyar A, Young K, et al. Leukaemia cell of origin identified by chromatin landscape of bulk tumour cells. Nat Commun 2016;7:12166.
25. Ng SW, Mitchell A, Kennedy JA, et al. A 17-gene stemness score for rapid determination of risk in acute leukaemia. Nature 2016;540:433-7.
27. Raffel S, Klimmeck D, Falcone M, et al. Quantitative proteomics reveals specific metabolic features of acute myeloid leukemia stem cells. Blood 2020;136:1507-19.
28. Harris MH, Thompson CB. The role of the Bcl-2 family in the regulation of outer mitochondrial membrane permeability. Cell Death Differ 2000;7:1182-91.
29. Heiden MG, Chandel NS, Schumacker PT, Thompson CB. Bcl-xL prevents cell death following growth factor withdrawal by facilitating mitochondrial ATP/ADP exchange. Mol Cell 1999;3:159-67.
30. Manfredi G, Kwong JQ, Oca-Cossio JA, et al. BCL-2 improves oxidative phosphorylation and modulates adenine nucleotide translocation in mitochondria of cells harboring mutant mtDNA. J Biol Chem 2003;278:5639-45.
31. Johnson EA, Marks RS, Mandrekar SJ, et al. Phase III randomized, double-blind study of maintenance CAI or placebo in patients with advanced non-small cell lung cancer (NSCLC) after completion of initial therapy (NCCTG 97-24-51). Lung Cancer 2008;60:200-7.
32. Ellinghaus P, Heisler I, Unterschemmann K, et al. BAY 87-2243, a highly potent and selective inhibitor of hypoxia-induced gene activation has antitumor activities by inhibition of mitochondrial complex I. Cancer Med 2013;2:611-24.
33. Tan AS, Baty JW, Dong LF, et al. Mitochondrial genome acquisition restores respiratory function and tumorigenic potential of cancer cells without mitochondrial DNA. Cell Metab 2015;21:81-94.
34. Saito K, Zhang Q, Yang H, et al. Exogenous mitochondrial transfer and endogenous mitochondrial fission facilitate AML resistance to OxPhos inhibition. Blood Adv 2021;5:4233-55.
35. Abounit S, Delage E, Zurzolo C. Identification and characterization of tunneling nanotubes for intercellular trafficking. Curr Protoc Cell Biol 2015;67:12.0.1-.0.21.
36. Biran A, Perelmutter M, Gal H, et al. Senescent cells communicate via intercellular protein transfer. Genes Dev 2015;29:791-802.
37. Frei DM, Hodneland E, Rios-Mondragon I, et al. Novel microscopy-based screening method reveals regulators of contact-dependent intercellular transfer. Sci Rep 2015;5:12879.
39. Mistry JJ, Marlein CR, Moore JA, et al. ROS-mediated PI3K activation drives mitochondrial transfer from stromal cells to hematopoietic stem cells in response to infection. Proc Natl Acad Sci USA 2019;116:24610-9.
41. Kim DY, Jung SY, Kim YJ, et al. Hypoxia-dependent mitochondrial fission regulates endothelial progenitor cell migration, invasion, and tube formation. Korean J Physiol Pharmacol 2018;22:203-13.
42. Toyama EQ, Herzig S, Courchet J, et al. Metabolism. AMP-activated protein kinase mediates mitochondrial fission in response to energy stress. Science 2016;351:275-81.
43. Cai J, Wang J, Huang Y, et al. ERK/Drp1-dependent mitochondrial fission is involved in the MSC-induced drug resistance of T-cell acute lymphoblastic leukemia cells. Cell Death Dis 2016;7:e2459.
44. Pei S, Minhajuddin M, Adane B, et al. AMPK/FIS1-mediated mitophagy is required for self-renewal of human AML stem cells. Cell Stem Cell 2018;23:86-100.e6.
45. Wallace DC. Mitochondria and cancer: warburg addressed. Cold Spring Harb Symp Quant Biol 2005;70:363-74.
46. Marlein CR, Zaitseva L, Piddock RE, et al. NADPH oxidase-2 derived superoxide drives mitochondrial transfer from bone marrow stromal cells to leukemic blasts. Blood 2017;130:1649-60.
47. Jones CL, Stevens BM, D'Alessandro A, et al. Inhibition of amino acid metabolism selectively targets human leukemia stem cells. Cancer Cell 2018;34:724-40.e4.
48. Schimmer AD. Novel mitochondrial mechanisms of cytarabine resistance in primary AML cells. Cancer Discov 2017;7:670-2.
49. Syed N, Langer J, Janczar K, et al. Epigenetic status of argininosuccinate synthetase and argininosuccinate lyase modulates autophagy and cell death in glioblastoma. Cell Death Dis 2013;4:e458.
50. Xing P, Liao Z, Ren Z, et al. Roles of low-density lipoprotein receptor-related protein 1 in tumors. Chin J Cancer 2016;35:6.
51. Grosso RA, Caldarone PVS, Sanchez MC, Chiabrando GA, Colombo MI, Fader CM. Hemin induces autophagy in a leukemic erythroblast cell line through the LRP1 receptor. Biosci Rep 2019:39.
52. Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD. Metformin and reduced risk of cancer in diabetic patients. BMJ 2005;330:1304-5.
53. Andrzejewski S, Gravel SP, Pollak M, St-Pierre J. Metformin directly acts on mitochondria to alter cellular bioenergetics. Cancer Metab 2014;2:12.
54. Scotland S, Saland E, Skuli N, et al. Mitochondrial energetic and AKT status mediate metabolic effects and apoptosis of metformin in human leukemic cells. Leukemia 2013;27:2129-38.
55. Stuart SD, Schauble A, Gupta S, et al. A strategically designed small molecule attacks alpha-ketoglutarate dehydrogenase in tumor cells through a redox process. Cancer Metab 2014;2:4.
56. Zachar Z, Marecek J, Maturo C, et al. Non-redox-active lipoate derivates disrupt cancer cell mitochondrial metabolism and are potent anticancer agents in vivo. J Mol Med 2011;89:1137-48.
57. Pardee TS, Luther S, Buyse M, Powell BL, Cortes J. Devimistat in combination with high dose cytarabine and mitoxantrone compared with high dose cytarabine and mitoxantrone in older patients with relapsed/refractory acute myeloid leukemia: ARMADA 2000 Phase III study. Future Oncol 2019;15:3197-208.
58. Anderson R, Miller LD, Isom S, et al. Phase II trial of cytarabine and mitoxantrone with devimistat in acute myeloid leukemia. Nat Commun 2022;13:1673.
59. Behan JW, Yun JP, Proektor MP, et al. Adipocytes impair leukemia treatment in mice. Cancer Res 2009;69:7867-74.
60. Justesen J, Stenderup K, Ebbesen EN, Mosekilde L, Steiniche T, Kassem M. Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis. Biogerontology 2001;2:165-71.
61. Magome T, Froelich J, Holtan SG, et al. Whole-body distribution of leukemia and functional total marrow irradiation based on FLT-PET and dual-energy CT. Mol Imaging 2017;16:1536012117732203.
62. Islam MS, Stemig ME, Takahashi Y, Hui SK. Radiation response of mesenchymal stem cells derived from bone marrow and human pluripotent stem cells. J Radiat Res 2015;56:269-77.
63. Nieman KM, Kenny HA, Penicka CV, et al. Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat Med 2011;17:1498-503.
64. Carracedo A, Cantley LC, Pandolfi PP. Cancer metabolism: fatty acid oxidation in the limelight. Nat Rev Cancer 2013;13:227-32.
65. Pepino MY, Kuda O, Samovski D, Abumrad NA. Structure-function of CD36 and importance of fatty acid signal transduction in fat metabolism. Annu Rev Nutr 2014;34:281-303.
66. Farge T, Saland E, de Toni F, et al. Chemotherapy-resistant human acute myeloid leukemia cells are not enriched for leukemic stem cells but require oxidative metabolism. Cancer Discov 2017;7:716-35.
67. Ricciardi MR, Mirabilii S, Allegretti M, et al. Targeting the leukemia cell metabolism by the CPT1a inhibition: functional preclinical effects in leukemias. Blood 2015;126:1925-9.
68. Itoh T, Fairall L, Amin K, et al. Structural basis for the activation of PPARgamma by oxidized fatty acids. Nat Struct Mol Biol 2008;15:924-31.
69. Tabe Y, Yamamoto S, Saitoh K, et al. Bone marrow adipocytes facilitate fatty acid oxidation activating AMPK and a transcriptional network supporting survival of acute monocytic leukemia cells. Cancer Res 2017;77:1453-64.
70. Ye H, Adane B, Khan N, et al. Leukemic stem cells evade chemotherapy by metabolic adaptation to an adipose tissue niche. Cell Stem Cell 2016;19:23-37.
71. Shafat MS, Oellerich T, Mohr S, et al. Leukemic blasts program bone marrow adipocytes to generate a protumoral microenvironment. Blood 2017;129:1320-32.
72. Pascual G, Avgustinova A, Mejetta S, et al. Targeting metastasis-initiating cells through the fatty acid receptor CD36. Nature 2017;541:41-5.
73. Balaban S, Shearer RF, Lee LS, et al. Adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration. Cancer Metab 2017;5:1.
74. Zhang M, Di Martino JS, Bowman RL, et al. Adipocyte-derived lipids mediate melanoma progression via FATP proteins. Cancer Discov 2018;8:1006-25.
75. Nieman KM, Romero IL, Van Houten B, Lengyel E. Adipose tissue and adipocytes support tumorigenesis and metastasis. Biochim Biophys Acta 2013;1831:1533-41.
77. Sengenes C, Bouloumie A, Hauner H, et al. Involvement of a cGMP-dependent pathway in the natriuretic peptide-mediated hormone-sensitive lipase phosphorylation in human adipocytes. J Biol Chem 2003;278:48617-26.
78. Yamauchi T, Kamon J, Minokoshi Y, et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 2002;8:1288-95.
79. Alers S, Löffler AS, Wesselborg S, Stork B. Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: cross talk, shortcuts, and feedbacks. Mol Cell Biol 2012;32:2-11.
80. Cawthorn WP, Scheller EL, Learman BS, et al. Bone marrow adipose tissue is an endocrine organ that contributes to increased circulating adiponectin during caloric restriction. Cell Metab 2014;20:368-75.
81. Medina EA, Oberheu K, Polusani SR, Ortega V, Velagaleti GV, Oyajobi BO. PKA/AMPK signaling in relation to adiponectin’s antiproliferative effect on multiple myeloma cells. Leukemia 2014;28:2080-9.
82. Ma R, Yu D, Peng Y, et al. Resveratrol induces AMPK and mTOR signaling inhibition-mediated autophagy and apoptosis in multiple myeloma cells. Acta Biochim Biophys Sin 2021;53:775-83.
83. Chaffer CL, Brueckmann I, Scheel C, et al. Normal and neoplastic nonstem cells can spontaneously convert to a stem-like state. Proc Natl Acad Sci USA 2011;108:7950-5.
84. Samudio I, Harmancey R, Fiegl M, et al. Pharmacologic inhibition of fatty acid oxidation sensitizes human leukemia cells to apoptosis induction. J Clin Invest 2010;120:142-56.
85. Jones CL, Stevens BM, D'Alessandro A, et al. Inhibition of amino acid metabolism selectively targets human leukemia stem cells. Cancer Cell 2019;35:333-5.
86. Stevens BM, Jones CL, Pollyea DA, et al. Fatty acid metabolism underlies venetoclax resistance in acute myeloid leukemia stem cells. Nat Cancer 2020;1:1176-87.
87. Tabe Y, Saitoh K, Yang H, et al. Inhibition of FAO in AML co-cultured with BM adipocytes: mechanisms of survival and chemosensitization to cytarabine. Sci Rep 2018;8:16837.
88. Pike LS, Smift AL, Croteau NJ, Ferrick DA, Wu M. Inhibition of fatty acid oxidation by etomoxir impairs NADPH production and increases reactive oxygen species resulting in ATP depletion and cell death in human glioblastoma cells. Biochim Biophys Acta 2011;1807:726-34.
89. Schreurs M, Kuipers F, van der Leij FR. Regulatory enzymes of mitochondrial beta-oxidation as targets for treatment of the metabolic syndrome. Obes Rev 2010;11:380-8.
90. Shim JK, Choi S, Yoon SJ, et al. Etomoxir, a carnitine palmitoyltransferase 1 inhibitor, combined with temozolomide reduces stemness and invasiveness in patient-derived glioblastoma tumorspheres. Cancer Cell Int 2022;22:309.
91. Wang T, Fahrmann JF, Lee H, et al. JAK/STAT3-regulated fatty acid β-oxidation is critical for breast cancer stem cell self-renewal and chemoresistance. Cell Metab 2018;27:1357.
92. Dhakal B, Li CMY, Li R, et al. The antianginal drug perhexiline displays cytotoxicity against colorectal cancer cells in vitro: a potential for drug repurposing. Cancers 2022;14:1043.
93. Lee EA, Angka L, Rota SG, et al. Targeting mitochondria with avocatin B induces selective leukemia cell death. Cancer Res 2015;75:2478-88.
94. Tcheng M, Samudio I, Lee EA, Minden MD, Spagnuolo PA. The mitochondria target drug avocatin B synergizes with induction chemotherapeutics to induce leukemia cell death. Leuk Lymphoma 2017;58:986-8.
95. Tcheng M, Roma A, Ahmed N, et al. Very long chain fatty acid metabolism is required in acute myeloid leukemia. Blood 2021;137:3518-32.
96. Mesbahi Y, Trahair TN, Lock RB, Connerty P. Exploring the metabolic landscape of AML: from haematopoietic stem cells to myeloblasts and leukaemic stem cells. Front Oncol 2022;12:807266.
97. Zhang Y, Li F, Patterson AD, et al. Abcb11 deficiency induces cholestasis coupled to impaired β-fatty acid oxidation in mice. J Biol Chem 2012;287:24784-94.
