1. Papaemmanuil E, Gerstung M, Bullinger L, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med.
2016;374(23):2209-2221.
2. Freeman SD, Hills RK, Virgo P, et al. Measurable residual disease
at induction redefines partial response in acute myeloid leukemia
and stratifies outcomes in patients at standard risk without NPM1
mutations. J Clin Oncol. 2018;36(15):1486-1497.
3. Perl AE, Martinelli G, Cortes JE, et al. Gilteritinib or chemotherapy for relapsed or refractory FLT3-mutated AML. N Engl J Med.
2019;381(18):1728-1740.
4. Warburg O. On the origin of cancer cells. Science.
1956;123(3191):309-314.
5. Baccelli I, Gareau Y, Lehnertz B, et al. Mubritinib targets the
electron transport chain complex I and reveals the landscape of
OXPHOS dependency in acute myeloid leukemia. Cancer Cell.
2019;36(1):84-99.
6. Molina JR, Sun Y, Protopopova M, et al. An inhibitor of oxidative phosphorylation exploits cancer vulnerability. Nat Med.
2018;24(7):1036-1046.
7. Roesch A, Vultur A, Bogeski I, et al. Overcoming intrinsic multidrug resistance in melanoma by blocking the mitochondrial respiratory chain of slow-c ycling JARID1B(high) cells. Cancer Cell.
2013;23(6):811-825.
8. Bonnay F, Veloso A, Steinmann V, et al. Oxidative metabolism
drives immortalization of neural stem cells during tumorigenesis.
Cell. 2020;182(6):1490-1507.
9. Sancho P, Burgos-Ramos E, Tavera A, et al. MYC/PGC-1α balance
determines the metabolic phenotype and plasticity of pancreatic
cancer stem cells. Cell Metab. 2015;22(4):590-605.
10. Skrtić M, Sriskanthadevan S, Jhas B, et al. Inhibition of mitochondrial translation as a therapeutic strategy for human acute myeloid
leukemia. Cancer Cell. 2011;20(5):674-688.
11. Cole A, Wang Z, Coyaud E, et al. Inhibition of the mitochondrial
protease ClpP as a therapeutic strategy for human acute myeloid
leukemia. Cancer Cell. 2015;27(6):864-876.
12. Sriskanthadevan S, Jeyaraju DV, Chung TE, et al. AML cells have
low spare reserve capacity in their respiratory chain that renders them susceptible to oxidative metabolic stress. Blood.
2015;125(13):2120-2130.
13. Kuntz EM, Baquero P, Michie AM, et al. Targeting mitochondrial
oxidative phosphorylation eradicates therapy-resistant chronic
myeloid leukemia stem cells. Nat Med. 2017;23(10):1234-1240.
14. Pollyea DA, Stevens BM, Jones CL, et al. Venetoclax with azacitidine
disrupts energy metabolism and targets leukemia stem cells in patients with acute myeloid leukemia. Nat Med. 2018;24(12):1859-1866.
15. DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and Venetoclax
in previously untreated acute myeloid leukemia. N Engl J Med.
2020;383(7):617-629.
16. Sykes DB, Kfoury YS, Mercier FE, et al. Inhibition of dihydroorotate
dehydrogenase overcomes differentiation blockade in acute myeloid leukemia. Cell. 2016;167(1):171-186.
17. 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(1):86-100.
18. Panina SB, Baran N, Brasil da Costa FH, Konopleva M, Kirienko NV.
A mechanism for increased sensitivity of acute myeloid leukemia to
mitotoxic drugs. Cell Death Dis. 2019;10(8):617.
19. Vyas S, Zaganjor E, Haigis MC. Mitochondria and cancer. Cell.
2016;166(3):555-566.
20. Schrepfer E, Scorrano L. Mitofusins, from mitochondria to metabolism. Mol Cell. 2016;61(5):683-694.
21. 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(7):716-735.
22. Vriens K, Christen S, Parik S, et al. Evidence for an alternative fatty
acid desaturation pathway increasing cancer plasticity. Nature.
2019;566(7744):403-4 06.
23. Cheng X, Geng F, Pan M, et al. Targeting DGAT1 ameliorates glioblastoma by increasing fat catabolism and oxidative stress. Cell
Metab. 2020;32(2):229-242.
24. 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(16):1925-1929.
25. 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(1):23-37.
26. 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(6):1453-1464.
27. Jones CL, Stevens BM, D'Alessandro A, et al. Inhibition of amino
acid metabolism selectively targets human leukemia stem cells.
Cancer Cell. 2018;34(5):724-740.
28. Stevens BM, Jones CL, Pollyea DA, et al. Fatty acid metabolism underlies venetoclax resistance in acute myeloid leukemia stem cells.
Nat Cancer. 2020;1(12):1176-1187.
29. Kikushige Y, Miyamoto T, Kochi Y, et al. Human acute leukemia utilizes branched-chain amino acid catabolism to maintain stemness
through regulating PRC2 function. Blood Adv. 2022. Online ahead
of print.
3 0. Yu J, Loh K, Song ZY, Yang HQ, Zhang Y, Lin S. Update on glycerol-
3-phosphate acyltransferases: the roles in the development of insulin resistance. Nutr Diabetes. 2018;8(1):34.
31. Karasawa K, Tanigawa K, Harada A, Yamashita A. Transcriptional
regulation of acyl-CoA: glycerol-sn-3-phosphate acyltransferases.
Int J Mol Sci. 2019;20(4):964.
32. Ohba Y, Sakuragi T, Kage-Nakadai E, et al. Mitochondria-t ype GPAT
is required for mitochondrial fusion. EMBO J. 2013;32(9):1265-1279.
3 3. Faris R, Fan YY, De Angulo A, et al. Mitochondrial glycerol-
3-p hosphate acyltransferase-1 is essential for murine
CD4(+) T cell metabolic activation. Biochim Biophys Acta.
2014;1842(10):1475-1482.
3 4. de Almeida MJ, Luchsinger LL, Corrigan DJ, Williams LJ,
Snoeck HW. Dye-independent methods reveal elevated mitochondrial mass in hematopoietic stem cells. Cell Stem Cell.
2017;21(6):725-729.
35. Filippi MD, Ghaffari S. Mitochondria in the maintenance of hematopoietic stem cells: new perspectives and opportunities. Blood.
2019;133(18):1943-1952.
36. Fonseca TB, Sánchez-Guerrero Á, Milosevic I, Raimundo N.
Mitochondrial fission requires DRP1 but not dynamins. Nature.
2019;570(7761):E34-E42.
37. Giacomello M, Pyakurel A, Glytsou C, Scorrano L. The cell biology of mitochondrial membrane dynamics. Nat Rev Mol Cell Biol.
2020;21(4):204-224.
38. Wydysh EA, Medghalchi SM, Vadlamudi A, Townsend CA. Design
and synthesis of small molecule glycerol 3-phosphate acyltransferase inhibitors. J Med Chem. 2009;52(10):3317-3327.
39. Kuhajda FP, Aja S, Tu Y, et al. Pharmacological glycerol-3-phosphate
acyltransferase inhibition decreases food intake and adiposity and
increases insulin sensitivity in diet-induced obesity. Am J Physiol
Regul Integr Comp Physiol. 2011;301(1):R116-R130.
12 4 0. McFadden JW, Aja S, Li Q, et al. Increasing fatty acid oxidation remodels the hypothalamic neurometabolome to mitigate stress and
inflammation. PLoS One. 2014;9(12):e115642.
41. Bosc C, Broin N, Fanjul M, et al. Autophagy regulates fatty acid
availability for oxidative phosphorylation through mitochondria-
endoplasmic reticulum contact sites. Nat Commun. 2020;11(1):4056.
42. Meleh M, Pozlep B, Mlakar A, et al. Determination of serum lysophosphatidic acid as a potential biomarker for ovarian cancer. J
Chromatogr B Analyt Technol Biomed Life Sci. 2007;858(1–2):287-291.
43. Archer SL. Mitochondrial dynamics —mitochondrial fission and fusion in human diseases. N Engl J Med. 2013;369(23):2236-2251.
4 4. Ma Y, Wang L, Jia R. The role of mitochondrial dynamics in human
cancers. Am J Cancer Res. 2020;10(5):1278-1293.
45. Adachi Y, Itoh K, Yamada T, et al. Coincident phosphatidic acid
interaction restrains Drp1 in mitochondrial division. Mol Cell.
2016;63(6):1034-1043.
IRIFUNE et al.
S U P P O R T I N G I N FO R M AT I O N
Additional supporting information can be found online in the
Supporting Information section at the end of this article.
How to cite this article: Irifune H, Kochi Y, Miyamoto T, et al.
GPAM mediated lysophosphatidic acid synthesis regulates
mitochondrial dynamics in acute myeloid leukemia. Cancer
Sci. 2023;00:1-12. doi:10.1111/cas.15835
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