Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T, et al. Prognosis and administration of AML in adults: 2017 ELN suggestions from a global skilled panel. Blood. 2017;129:424–47.
Lyman SD, James L, Bos TV, de Vries P, Brasel Ok, Gliniak B, et al. Molecular cloning of a ligand for the flt3 flk-2 tyrosine kinase receptor: a proliferative issue for primitive hematopoietic cells. Cell. 1993;75:1157–67.
Mizuki M, Fenski R, Halfter H, Matsumura I, Schmidt R, Müller C, et al. Flt3 mutations from sufferers with acute myeloid leukemia induce transformation of 32D cells mediated by the Ras and STAT5 pathways. Blood. 2000;96:3907–14.
Nakao M, Yokota S, Iwai T, Kaneko H, Horiike S, Kashima Ok, et al. Inside tandem duplication of the flt3 gene present in acute myeloid leukemia. Leukemia. 1996;10:1911–8.
Daver N, Schlenk RF, Russell NH, Levis MJ. Concentrating on FLT3 mutations in AML: assessment of present information and proof. Leukemia. 2019;33:299–312.
Stone RM, Mandrekar SJ, Sanford BL, Laumann Ok, Geyer S, Bloomfield CD, et al. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N. Engl J Med. 2017;377:454–64.
Serve H, Krug U, Wagner R, Sauerland MC, Heinecke A, Brunnberg U, et al. Sorafenib together with intensive chemotherapy in aged sufferers with acute myeloid leukemia: outcomes from a randomized, placebo-controlled trial. J Clin Oncol. 2013;31:3110–8.
Röllig C, Serve H, Hüttmann A, Noppeney R, Müller-Tidow C, Krug U, et al. Addition of sorafenib versus placebo to plain remedy in sufferers aged 60 years or youthful with newly identified acute myeloid leukaemia (SORAML): a multicentre, section 2, randomised managed trial. Lancet Oncol. 2015;16:1691–9.
Smith CC, Wang Q, Chin CS, Salerno S, Damon LE, Levis MJ, et al. Validation of ITD mutations in FLT3 as a therapeutic goal in human acute myeloid leukaemia. Nature. 2012;485:260–3.
Smith CC, Paguirigan A, Jeschke GR, Lin KC, Massi E, Tarver T, et al. Heterogeneous resistance to quizartinib in acute myeloid leukemia revealed by single-cell evaluation. Blood. 2017;130:48–58.
Warburg O, Wind F, Negelein E. The metabolism of tumors within the physique. J Gen Physiol. 1927;8:519–30.
Warburg O. On the origin of most cancers cells. Science (1979). 1956;123:309–14.
Chen WL, Wang JH, Zhao AH, Xu X, Wang YH, Chen TL, et al. A definite glucose metabolism signature of acute myeloid leukemia with prognostic worth. Blood. 2014;124:1645–54.
Ju HQ, Zhan G, Huang A, Solar Y, Wen S, Yang J, et al. ITD mutation in FLT3 tyrosine kinase promotes Warburg impact and renders therapeutic sensitivity to glycolytic inhibition. Leukemia. 2017;31:2143–50.
DeBerardinis RJ, Chandel NS. We have to discuss in regards to the Warburg impact. Nat Metab. 2020;2:127–9.
Koppenol WH, Bounds PL, Dang CV. Otto Warburg’s contributions to present ideas of most cancers metabolism. Nat Rev Most cancers. 2011;11:325–37.
Weinberg F, Hamanaka R, Wheaton WW, Weinberg S, Joseph J, Lopez M, et al. Mitochondrial metabolism and ROS technology are important for Kras-mediated tumorigenicity. Proc Natl Acad Sci. 2010;107:8788–93.
Marin-Valencia I, Yang C, Mashimo T, Cho S, Baek H, Yang XL, et al. Evaluation of tumor metabolism reveals mitochondrial glucose oxidation in genetically numerous human glioblastomas within the mouse mind in vivo. Cell Metab. 2012;15:827–37.
Guo JY, Chen HY, Mathew R, Fan J, Strohecker AM, Karsli-Uzunbas G, et al. Activated Ras requires autophagy to take care of oxidative metabolism and tumorigenesis. Genes Dev. 2011;25:460–70.
Kreitz J, Schönfeld C, Seibert M, Stolp V, Alshamleh I, Oellerich T, et al. Metabolic plasticity of acute myeloid leukemia. Cells. 2019;8:805.
Weinberg SE, Chandel NS. Concentrating on mitochondria metabolism for most cancers remedy. Nat Chem Biol. 2015;11:9–15.
Caro P, Kishan AU, Norberg E, Stanley IA, Chapuy B, Ficarro SB, et al. Metabolic signatures uncover distinct targets in molecular subsets of diffuse massive B cell lymphoma. Most cancers Cell. 2012;22:547–60.
Haq R, Shoag J, Andreu-Perez P, Yokoyama S, Edelman H, Rowe GC, et al. Oncogenic BRAF regulates oxidative metabolism by way of PGC1α and MITF. Most cancers Cell. 2013;23:302–15.
Baccelli I, Gareau Y, Lehnertz B, Gingras S, Spinella JF, Corneau S, et al. Mubritinib targets the electron transport chain complicated I and divulges the panorama of OXPHOS dependency in acute myeloid leukemia. Most cancers Cell. 2019;36:84–99.
Farge T, Saland E, de Toni F, Aroua N, Hosseini M, Perry R, et al. Chemotherapy-resistant human acute myeloid leukemia cells should not enriched for leukemic stem cells however require oxidative metabolism. Most cancers Discov. 2017;7:716–35.
Pollyea DA, Stevens BM, Jones CL, Winters A, Pei S, Minhajuddin M, et al. Venetoclax with azacitidine disrupts vitality metabolism and targets leukemia stem cells in sufferers with acute myeloid leukemia. Nat Med. 2018;24:1859–66.
Roca-Portoles A, Rodriguez-Blanco G, Sumpton D, Cloix C, Mullin M, Mackay GM, et al. Venetoclax causes metabolic reprogramming unbiased of BCL-2 inhibition. Cell Demise Dis. 2020;11:1–13.
Molina JR, Solar Y, Protopopova M, Gera S, Bandi M, Bristow C, et al. An inhibitor of oxidative phosphorylation exploits most cancers vulnerability. Nat Med. 2018;24:1036–46.
Skrtic M, Sriskanthadevan S, Jhas B, Gebbia M, Wang X, Wang Z, et al. Inhibition of mitochondrial translation as a therapeutic technique for human acute myeloid leukemia. Most cancers Cell. 2011;20:674–88.
Sriskanthadevan S, Jeyaraju DV, Chung TE, Prabha S, Xu W, Skrtic M, et al. AML cells have low spare reserve capability of their respiratory chain that renders them prone to oxidative metabolic stress. Blood. 2015;125:2120–30.
Pardee TS, Anderson RG, Pladna KM, Isom S, Ghiraldeli LP, Miller LD, et al. A section I examine of CPI-613 together with high-dose cytarabine and mitoxantrone for relapsed or refractory acute myeloid leukemia. Clin Most cancers Res. 2018;24:2060–73.
Emadi A, Sadowska M, Carter-Cooper B, Bhatnagar V, van der Merwe I, Levis MJ, et al. Perturbation of mobile oxidative state induced by dichloroacetate and arsenic trioxide for therapy of acute myeloid leukemia. Leuk Res. 2015;39:719–29.
Roche TE, Baker JC, Yan X, Hiromasa Y, Gong X, Peng T, et al. Distinct regulatory properties of pyruvate dehydrogenase kinase and phosphatase isoforms. Prog Nucleic Acid Res Mol Biol. 2001;70:33–75.
Shan C, Kang HB, Elf S, Xie J, Gu TL, Aguiar M, et al. Tyr-94 phosphorylation inhibits pyruvate dehydrogenase phosphatase 1 and promotes tumor progress. J Biol Chem. 2014;289:21413–22.
Fan J, Shan C, Kang HB, Elf S, Xie J, Tucker M, et al. Tyr phosphorylation of PDP1 toggles recruitment between ACAT1 and SIRT3 to manage the pyruvate dehydrogenase complicated. Mol Cell. 2014;53:534–48.
Chen J, Guccini I, Di Mitri D, Brina D, Revandkar A, Sarti M, et al. Compartmentalized actions of the pyruvate dehydrogenase complicated maintain lipogenesis in prostate most cancers. Nat Genet. 2018;50:219–28.
Choudhary C, Schwäble J, Brandts C, Tickenbrock L, Sargin B, Kindler T, et al. AML-associated Flt3 kinase area mutations present sign transduction variations in contrast with Flt3 ITD mutations. Blood. 2005;106:265–73.
Ward NJ, Buckley SMK, Waddington SN, VandenDriessche T, Chuah MKL, Nathwani AC, et al. Codon optimization of human issue VIII cDNAs results in high-level expression. Blood [Internet]. 2011;117:798–807. https://doi.org/10.1182/blood-2010-05-282707.
Engler C, Kandzia R, Marillonnet S. A one pot, one step, precision cloning technique with excessive throughput functionality. PLoS One [Internet]. 2008;3:e3647. https://doi.org/10.1371/journal.pone.0003647.
Bhayadia R, Krowiorz Ok, Haetscher N, Jammal R, Emmrich S, Obulkasim A, et al. Endogenous tumor suppressor microRNA-193b: therapeutic and prognostic worth in acute myeloid leukemia. J Clin Oncol. 2018;36:1007–16.
Gallipoli P, Giotopoulos G, Tzelepis Ok, Costa ASH, Vohra S, Medina-Perez P, et al. Glutaminolysis is a metabolic dependency in FLT3ITD acute myeloid leukemia unmasked by FLT3 tyrosine kinase inhibition. Blood. 2018;131:1639–53.
Ludwig C, Günther UL. MetaboLab – superior NMR knowledge processing and evaluation for metabolomics. BMC Bioinforma. 2011;12:366.
Goddard Td, Kneller DG Sparky 3. College of California, San Francisco. San Francisco: College of California.
Alshamleh I, Krause N, Richter C, Kurrle N, Serve H, Günther UL, et al. Actual-time NMR spectroscopy for finding out metabolism. Angew Chem Int Ed. 2020;59:2304–8.
McCarthy DJ, Chen Y, Smyth GK. Differential expression evaluation of multifactor RNA-Seq experiments with respect to organic variation. Nucleic Acids Res. 2012;40:4288–97.
Ritchie ME, Phipson B, Wu D, Hu Y, Legislation CW, Shi W, et al. limma powers differential expression analyses for RNA-sequencing and microarray research. Nucleic Acids Res. 2015;43:e47.
Doench JG, Fusi N, Sullender M, Hegde M, Vaimberg EW, Donovan KF, et al. Optimized sgRNA design to maximise exercise and reduce off-target results of CRISPR-Cas9. Nat Biotechnol [Internet]. 2016;34:184–91. https://doi.org/10.1038/nbt.3437.
Li W, Köster J, Xu H, Chen CH, Xiao T, Liu JS, et al. High quality management, modeling, and visualization of CRISPR screens with MAGeCK-VISPR. Genome Biol [Internet]. 2015;16:281. https://doi.org/10.1186/s13059-015-0843-6.
Wang B, Wang M, Zhang W, Xiao T, Chen CH, Wu A, et al. Integrative evaluation of pooled CRISPR genetic screens utilizing MAGeCKFlute. Nat Protoc [Internet]. 2019;14:756–80. https://doi.org/10.1038/s41596-018-0113-7.
Choudhary C, Olsen JV, Brandts C, Cox J, Reddy PNG, Böhmer FD, et al. Mislocalized activation of oncogenic RTKs switches downstream signaling outcomes. Mol Cell. 2009;36:326–39.
Wang Y, An H, Liu T, Qin C, Sesaki H, Guo S, et al. Metformin improves mitochondrial respiratory exercise by activation of AMPK. Cell Rep. 2019;29:1511–23.e5.
Jayavelu AK, Wolf S, Buettner F, Alexe G, Häupl B, Comoglio F, et al. The proteogenomic subtypes of acute myeloid leukemia. Most cancers Cell [Internet]. 2022;40:301–17.e12. https://www.sciencedirect.com/science/article/pii/S1535610822000587.
de Boer B, Prick J, Pruis MG, Keane P, Imperato MR, Jaques J, et al. Potential isolation and characterization of genetically and functionally distinct AML subclones. Most cancers Cell [Internet]. 2018;34:674–89.e8. https://doi.org/10.1016/j.ccell.2018.08.014.
DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, et al. Azacitidine and venetoclax in beforehand untreated acute myeloid leukemia. N. Engl J Med. 2020;383:617–29.
Cole A, Wang Z, Coyaud E, Voisin V, Gronda M, Jitkova Y, et al. Inhibition of the mitochondrial protease ClpP as a therapeutic technique for human acute myeloid leukemia. Most cancers Cell. 2015;27:864–76.
Erdem A, Marin S, Pereira-Martins DA, Cortés R, Cunningham A, Pruis MG, et al. The Glycolytic Gatekeeper PDK1 defines totally different metabolic states between genetically distinct subtypes of human acute myeloid leukemia. Nat Commun [Internet]. 2022;13:1105. https://doi.org/10.1038/s41467-022-28737-3.
Köthe S, Müller JP, Böhmer SA, Tschongov T, Fricke M, Koch S, et al. Options of Ras activation by a mislocalized oncogenic tyrosine kinase: FLT3 ITD alerts by Ok-Ras on the plasma membrane of acute myeloid leukemia cells. J Cell Sci. 2013;126:4746–55.
Decroocq J, Birsen R, Montersino C, Chaskar P, Mano J, Poulain L, et al. RAS activation induces artificial lethality of MEK inhibition with mitochondrial oxidative metabolism in acute myeloid leukemia. Leuk [Internet]. 2022;36:1237–52. https://doi.org/10.1038/s41375-022-01541-0.
Goto M, Miwa H, Suganuma Ok, Tsunekawa-Imai N, Shikami M, Mizutani M, et al. Adaptation of leukemia cells to hypoxic situation by switching the vitality metabolism or avoiding the oxidative stress. BMC Most cancers. 2014;14:1–9.
Ye H, Biniam A, Nabilah Ok, Timothy S, Minhajuddin M, Gasparetto M, et al. Leukemic stem cells evade chemotherapy by metabolic adaptation to an adipose tissue area of interest. Cell Stem Cell. 2016;19:23–37.
Suda T, Takubo Ok, Semenza GL. Metabolic regulation of hematopoietic stem cells within the hypoxic area of interest. Stem Cell. 2011;9:298–310.
Takubo Ok, Nagamatsu G, Kobayashi CI, Nakamura-Ishizu A, Kobayashi H, Ikeda E, et al. Regulation of glycolysis by Pdk features as a metabolic checkpoint for cell cycle quiescence in hematopoietic stem cells. Cell Stem Cell. 2013;12:49–61.
Yu WM, Liu X, Shen J, Jovanovic O, Pohl EE, Gerson SL, et al. Metabolic regulation by the mitochondrial phosphatase PTPMT1 is required for hematopoietic stem cell differentiation. Cell Stem Cell. 2013;12:62–74.
Tavor S, Petit I, Porozov S, Avigdor A, Dar A, Leider-Trejo L, et al. CXCR4 regulates migration and improvement of human acute myelogenous leukemia stem cells in transplanted NOD/SCID mice. Most cancers Res. 2004;64:2817–24.
Möhle R, Bautz F, Rafii S, Moore MA, Brugger W, Kanz L. The chemokine receptor CXCR-4 is expressed on CD34+ hematopoietic progenitors and leukemic cells and mediates transendothelial migration induced by stromal cell-derived factor-1. Blood. 1998;91:4523–30.
Jin L, Hope KJ, Zhai Q, Smadja-Joffe F, Dick JE. Concentrating on of CD44 eradicates human acute myeloid leukemic stem cells. Nat Med. 2006;12:1167–74.
Li Y, Shen J, Cheng CS, Gao H, Zhao J, Chen L. Overexpression of pyruvate dehydrogenase phosphatase 1 promotes the development of pancreatic adenocarcinoma by regulating energy-related AMPK/mTOR signaling. Cell Biosci. 2020;10:95.
Love LK, LeBlanc PJ, Inglis JG, Bradley NS, Choptiany J, Heigenhauser GJF, et al. The connection between human skeletal muscle pyruvate dehydrogenase phosphatase exercise and muscle cardio capability. J Appl Physiol. 2011;111:427–34.
Fisher-Wellman KH, Lin CT, Ryan TE, Reese LR, Gilliam LAA, Cathey BL, et al. Pyruvate dehydrogenase complicated and nicotinamide nucleotide transhydrogenase represent an energy-consuming redox circuit. Biochem J. 2015;467:271–80.
Henkenius Ok, Greene BH, Barckhausen C, Hartmann R, Marken M, Kaiser T, et al. Upkeep of mobile respiration signifies drug resistance in acute myeloid leukemia. Leuk Res. 2017;62:56–63.
Jones CL, Stevens BM, Pollyea DA, Culp-Hill R, Reisz JA, Nemkov T, et al. Nicotinamide metabolism mediates resistance to venetoclax in relapsed acute myeloid leukemia stem cells. Cell Stem Cell. 2020;27:748–64.e4.
Jones CL, Stevens BM, D’Alessandro A, Reisz JA, Culp-Hill R, Nemkov T, et al. Inhibition of amino acid metabolism selectively targets human leukemia stem cells. Most cancers Cell. 2018;34:724–40.e4.
Chen W, Drakos E, Grammatikakis I, Schlette EJ, Li J, Leventaki V, et al. mTOR signaling is activated by FLT3 kinase and promotes survival of FLT3- mutated acute myeloid leukemia cells. Mol Most cancers. 2010;9:292.
Poulain L, Sujobert P, Zylbersztejn F, Barreau S, Stuani L, Lambert M, et al. Excessive mTORC1 exercise drives glycolysis habit and sensitivity to G6PD inhibition in acute myeloid leukemia cells. Leukemia. 2017;31:2326–35.
