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ACUTE MYELOID LEUKEMIA

Ferritin-mediated mitochondrial iron homeostasis is essential for the survival of hematopoietic stem cells and leukemic stem cells

Leukemia (2024)Cite this article

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Abstract

Iron metabolism plays a crucial role in cell viability, but its relationship with adult stem cells and cancer stem cells is not fully understood. The ferritin complex, responsible for intracellular iron storage, is important in this process. We report that conditional deletion of ferritin heavy chain 1 (Fth1) in the hematopoietic system reduced the number and repopulation capacity of hematopoietic stem cells (HSCs). These effects were associated with a decrease in cellular iron level, leading to impaired mitochondrial function and the initiation of apoptosis. Iron supplementation, antioxidant, and apoptosis inhibitors reversed the reduced cell viability of Fth1-deleted hematopoietic stem and progenitor cells (HSPCs). Importantly, leukemic stem cells (LSCs) derived from MLL-AF9-induced acute myeloid leukemia (AML) mice exhibited reduced Fth1 expression, rendering them more susceptible to apoptosis induced by the iron chelation compared to normal HSPCs. Modulating FTH1 expression using mono-methyl fumarate increased LSCs resistance to iron chelator-induced apoptosis. Additionally, iron supplementation, antioxidant, and apoptosis inhibitors protected LSCs from iron chelator-induced cell death. Fth1 deletion also extended the survival of AML mice. These findings unveil a novel mechanism by which ferritin-mediated iron homeostasis regulates the survival of both HSCs and LSCs, suggesting potential therapeutic strategies for blood cancer with iron dysregulation.

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Fig. 1: Fth1 deletion impairs normal hematopoiesis.
Fig. 2: Fth1 deletion impairs HSCs self-renewal capacity in a ferroptosis-independent manner.
Fig. 3: A ferritin-mediated iron metabolism regulates apoptosis in HSPCs.
Fig. 4: Fth1 deletion reduces mitochondrial iron level which correlates with an impairment of mitochondrial function.
Fig. 5: Fth1 deletion limits the development of MLL-AF9-AML in mice.
Fig. 6: LSCs show higher sensitivity to iron restriction-induced apoptosis due to reduced FTH1 expression.

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Data availability

The RNA-seq data generated in this study have been deposited in the GEO database under accession code GSE240742. Source data are provided with this paper.

References

  1. Orkin SH, Zon LI. Hematopoiesis: an evolving paradigm for stem cell biology. Cell. 2008;132:631–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Wang J, Pantopoulos K. Regulation of cellular iron metabolism. Biochem J. 2011;434:365–81.

    Article  CAS  PubMed  Google Scholar 

  3. Gao G, Li J, Zhang Y, Chang YZ. Cellular iron metabolism and regulation. Adv Exp Med Biol. 2019;1173:21–32.

    Article  CAS  PubMed  Google Scholar 

  4. Dev S, Babitt JL. Overview of iron metabolism in health and disease. Hemodial Int. 2017;21:S6–S20.

    Article  PubMed  PubMed Central  Google Scholar 

  5. MacKenzie EL, Iwasaki K, Tsuji Y. Intracellular iron transport and storage: from molecular mechanisms to health implications. Antioxid Redox Signal. 2008;10:997–1030.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Bogdan AR, Miyazawa M, Hashimoto K, Tsuji Y. Regulators of iron homeostasis: new players in metabolism, cell death, and disease. Trends Biochem Sci. 2016;41:274–86.

    Article  CAS  PubMed  Google Scholar 

  7. Goldfarb AN, Freeman KC, Sahu RK, Elagib KE, Holy M, Arneja A, et al. Iron control of erythroid microtubule cytoskeleton as a potential target in treatment of iron-restricted anemia. Nat Commun. 2021;12:1645.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  8. al-Rafaie FN, Wilkes S, Wonke B, Hoffbrand AV. The effect of deferiprone (L1) and desferrioxamine on myelopoiesis using a liquid culture system. Br J Haematol. 1994;87:196–8.

    Article  CAS  PubMed  Google Scholar 

  9. Khan N, Downey J, Sanz J, Kaufmann E, Blankenhaus B, Pacis A, et al. M. tuberculosis reprograms hematopoietic stem cells to limit myelopoiesis and impair trained immunity. Cell. 2020;183:752–70.e22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Cabezas-Wallscheid N, Klimmeck D, Hansson J, Lipka DB, Reyes A, Wang Q, et al. Identification of regulatory networks in HSCs and their immediate progeny via integrated proteome, transcriptome, and DNA methylome analysis. Cell Stem Cell. 2014;15:507–22.

    Article  CAS  PubMed  Google Scholar 

  11. Bertoli S, Paubelle E, Berard E, Saland E, Thomas X, Tavitian S, et al. Ferritin heavy/light chain (FTH1/FTL) expression, serum ferritin levels, and their functional as well as prognostic roles in acute myeloid leukemia. Eur J Haematol. 2019;102:131–42.

    Article  CAS  PubMed  Google Scholar 

  12. Urrutia PJ, Mena NP, Nunez MT. The interplay between iron accumulation, mitochondrial dysfunction, and inflammation during the execution step of neurodegenerative disorders. Front Pharmacol. 2014;5:38.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Ward DM, Cloonan SM. Mitochondrial Iron in Human Health and Disease. Annu Rev Physiol. 2019;81:453–82.

    Article  CAS  PubMed  Google Scholar 

  14. Chang HC, Wu R, Shang M, Sato T, Chen C, Shapiro JS, et al. Reduction in mitochondrial iron alleviates cardiac damage during injury. EMBO Mol Med. 2016;8:247–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Corey SJ, Minden MD, Barber DL, Kantarjian H, Wang JC, Schimmer AD. Myelodysplastic syndromes: the complexity of stem-cell diseases. Nat Rev Cancer. 2007;7:118–29.

    Article  CAS  PubMed  Google Scholar 

  16. Paul BT, Manz DH, Torti FM, Torti SV. Mitochondria and Iron: current questions. Expert Rev Hematol. 2017;10:65–79.

    Article  CAS  PubMed  Google Scholar 

  17. Melenovsky V, Petrak J, Mracek T, Benes J, Borlaug BA, Nuskova H, et al. Myocardial iron content and mitochondrial function in human heart failure: a direct tissue analysis. Eur J Heart Fail. 2017;19:522–30.

    Article  CAS  PubMed  Google Scholar 

  18. Morganti C, Ito K. Mitochondrial Contributions to Hematopoietic Stem Cell Aging. Int J Mol Sci. 2021;22.

  19. Wang N, Yin J, You N, Yang S, Guo D, Zhao Y, et al. TWIST1 preserves hematopoietic stem cell function via the CACNA1B/Ca2+/mitochondria axis. Blood. 2021;137:2907–19.

    Article  CAS  PubMed  Google Scholar 

  20. Filippi MD, Ghaffari S. Mitochondria in the maintenance of hematopoietic stem cells: new perspectives and opportunities. Blood. 2019;133:1943–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Shvartsman M, Kikkeri R, Shanzer A, Cabantchik ZI. Non-transferrin-bound iron reaches mitochondria by a chelatorinaccessible mechanism: biological and clinical implications. Am J Physiol Cell Physiol. 2007;293:C1383–94.

    Article  CAS  PubMed  Google Scholar 

  22. Weber S, Parmon A, Kurrle N, Schnutgen F, Serve H. The Clinical Significance of Iron Overload and Iron Metabolism in Myelodysplastic Syndrome and Acute Myeloid Leukemia. Front Immunol. 2020;11:627662.

    Article  CAS  PubMed  Google Scholar 

  23. Yassin MA, Soliman A, De Sanctis V, Hmissi SM, Abdulla MAJ, Ekeibed Y, et al. The Impact of Iron Overload in Patients with Acute Leukemia and Myelodysplastic Syndrome on Hepatic and Endocrine functions. Acta Biomed. 2018;89:18–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Wang F, Lv H, Zhao B, Zhou L, Wang S, Luo J, et al. Iron and leukemia: new insights for future treatments. J Exp Clin Cancer Res. 2019;38:406.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Fang X, Cai Z, Wang H, Han D, Cheng Q, Zhang P, et al. Loss of Cardiac Ferritin H Facilitates Cardiomyopathy via Slc7a11-Mediated Ferroptosis. Circ Res. 2020;127:486–501.

    Article  CAS  PubMed  Google Scholar 

  26. Kakhlon O, Cabantchik ZI. The labile iron pool: characterization, measurement, and participation in cellular processes. Free Radic Biol Med. 2002;33:1037–46.

    Article  CAS  PubMed  Google Scholar 

  27. Ganz T. Systemic iron homeostasis. Physiol Rev. 2013;93:1721–41.

    Article  CAS  PubMed  Google Scholar 

  28. Li W, Jiang Z, Li T, Wei X, Zheng Y, Wu D, et al. Genome-wide analyses identify KLF4 as an important negative regulator in T-cell acute lymphoblastic leukemia through directly inhibiting T-cell associated genes. Mol Cancer. 2015;14:26.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Du J, Chen Y, Li Q, Han X, Cheng C, Wang Z, et al. HIF-1alpha deletion partially rescues defects of hematopoietic stem cell quiescence caused by Cited2 deficiency. Blood. 2012;119:2789–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Nosaka T, Kawashima T, Misawa K, Ikuta K, Mui AL, Kitamura T. STAT5 as a molecular regulator of proliferation, differentiation and apoptosis in hematopoietic cells. EMBO J. 1999;18:4754–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Di Stefano B, Collombet S, Jakobsen JS, Wierer M, Sardina JL, Lackner A, et al. C/EBPalpha creates elite cells for iPSC reprogramming by upregulating Klf4 and increasing the levels of Lsd1 and Brd4. Nat Cell Biol. 2016;18:371–81.

    Article  PubMed  Google Scholar 

  32. Garber M, Yosef N, Goren A, Raychowdhury R, Thielke A, Guttman M, et al. A high-throughput chromatin immunoprecipitation approach reveals principles of dynamic gene regulation in mammals. Mol Cell. 2012;47:810–22.

    Article  CAS  PubMed  Google Scholar 

  33. Li D, Hsu S, Purushotham D, Sears RL, Wang T. WashU Epigenome Browser update 2019. Nucleic Acids Res. 2019;47:W158–W65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Zhang D, Gao X, Li H, Borger DK, Wei Q, Yang E, et al. The microbiota regulates hematopoietic stem cell fate decisions by controlling iron availability in bone marrow. Cell Stem Cell. 2022;29:232–47 e7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Wu A, Feng B, Yu J, Yan L, Che L, Zhuo Y, et al. Fibroblast growth factor 21 attenuates iron overload-induced liver injury and fibrosis by inhibiting ferroptosis. Redox Biol. 2021;46:102131.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Sukumaran A, Chang J, Han M, Mintri S, Khaw BA, Kim J. Iron overload exacerbates age-associated cardiac hypertrophy in a mouse model of hemochromatosis. Sci Rep. 2017;7:5756.

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  37. Wang J, Lee J, Liem D, Ping P. HSPA5 Gene encoding Hsp70 chaperone BiP in the endoplasmic reticulum. Gene. 2017;618:14–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Stricher F, Macri C, Ruff M, Muller S. HSPA8/HSC70 chaperone protein: structure, function, and chemical targeting. Autophagy. 2013;9:1937–54.

    Article  CAS  PubMed  Google Scholar 

  39. Minoia M, Grit C, Kampinga HH. HSPA1A-independent suppression of PARK2 C289G protein aggregation by human small heat shock proteins. Mol Cell Biol. 2014;34:3570–8.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Rabdano SO, Izmailov SA, Luzik DA, Groves A, Podkorytov IS, Skrynnikov NR. Onset of disorder and protein aggregation due to oxidation-induced intermolecular disulfide bonds: case study of RRM2 domain from TDP-43. Sci Rep. 2017;7:11161.

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  41. Sebastian VP, Salazar GA, Coronado-Arrazola I, Schultz BM, Vallejos OP, Berkowitz L, et al. Heme Oxygenase-1 as a Modulator of Intestinal Inflammation Development and Progression. Front Immunol. 2018;9:1956.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Aratani Y. Myeloperoxidase: Its role for host defense, inflammation, and neutrophil function. Arch Biochem Biophys. 2018;640:47–52.

    Article  CAS  PubMed  Google Scholar 

  43. Kasai S, Mimura J, Ozaki T, Itoh K. Emerging Regulatory Role of Nrf2 in Iron, Heme, and Hemoglobin Metabolism in Physiology and Disease. Front Vet Sci. 2018;5:242.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Ito K, Hirao A, Arai F, Takubo K, Matsuoka S, Miyamoto K, et al. Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Nat Med. 2006;12:446–51.

    Article  CAS  PubMed  Google Scholar 

  45. Mendelson A, Frenette PS. Hematopoietic stem cell niche maintenance during homeostasis and regeneration. Nat Med. 2014;20:833–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Oakes SA, Scorrano L, Opferman JT, Bassik MC, Nishino M, Pozzan T, et al. Proapoptotic BAX and BAK regulate the type 1 inositol trisphosphate receptor and calcium leak from the endoplasmic reticulum. Proc Natl Acad Sci USA. 2005;102:105–10.

    Article  ADS  CAS  PubMed  Google Scholar 

  47. Rong YP, Aromolaran AS, Bultynck G, Zhong F, Li X, McColl K, et al. Targeting Bcl-2-IP3 receptor interaction to reverse Bcl-2's inhibition of apoptotic calcium signals. Mol Cell. 2008;31:255–65 43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Wang S, He X, Wu Q, Jiang L, Chen L, Yu Y, et al. Transferrin receptor 1-mediated iron uptake plays an essential role in hematopoiesis. Haematologica. 2020;105:2071–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017;45:W98–W102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Wang K, Wang M, Liao X, Gao S, Hua J, Wu X, et al. Locally organised and activated Fth1hi neutrophils aggravate inflammation of acute lung injury in an IL-10-dependent manner. Nat Commun. 2022;13:7703.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  51. Wessling-Resnick M. Iron homeostasis and the inflammatory response. Annu Rev Nutr. 2010;30:105–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Siegert I, Schodel J, Nairz M, Schatz V, Dettmer K, Dick C, et al. Ferritin-Mediated Iron Sequestration Stabilizes Hypoxia- Inducible Factor-1alpha upon LPS Activation in the Presence of Ample Oxygen. Cell Rep. 2015;13:2048–55.

    Article  CAS  PubMed  Google Scholar 

  53. Kerins MJ, Vashisht AA, Liang BX, Duckworth SJ, Praslicka BJ, Wohlschlegel JA, et al. Fumarate mediates a chronic proliferative signal in fumarate hydratase-inactivated cancer cells by increasing transcription and translation of ferritin genes. Mol Cell Biol. 2017;3 7:e00079–17.

    Google Scholar 

  54. Dowdle WE, Nyfeler B, Nagel J, Elling RA, Liu S, Triantafellow E, et al. Selective VPS34 inhibitor blocks autophagy and uncovers a role for NCOA4 in ferritin degradation and iron homeostasis in vivo. Nat Cell Biol. 2014;16:1069–79.

    Article  CAS  PubMed  Google Scholar 

  55. Mancias JD, Wang X, Gygi SP, Harper JW, Kimmelman AC. Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy. Nature. 2014;509:105–9.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  56. Muto Y, Nishiyama M, Nita A, Moroishi T, Nakayama KI. Essential role of FBXL5-mediated cellular iron homeostasis in maintenance of hematopoietic stem cells. Nat Commun. 2017;8:16114.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  57. Zhao J, Jia Y, Mahmut D, Deik AA, Jeanfavre S, Clish CB, et al. Human hematopoietic stem cell vulnerability to ferroptosis. Cell. 2023;186:732–47 e16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Hu Q, Zhang Y, Lou H, Ou Z, Liu J, Duan W, et al. GPX4 and vitamin E cooperatively protect hematopoietic stem and progenitor cells from lipid peroxidation and ferroptosis. Cell Death Dis. 2021;12:706.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Kao YR, Chen J, Narayanagari SR, Todorova TI, Aivalioti MM, Ferreira M, et al. Thrombopoietin receptor-independent stimulation of hematopoietic stem cells by eltrombopag. Sci Transl Med. 2018;10.

  60. He H, Qiao Y, Zhou Q, Wang Z, Chen X, Liu D, et al. Iron Overload Damages the Endothelial Mitochondria via the ROS/ADMA/DDAHII/eNOS/NO Pathway. Oxid Med Cell Longev. 2019;2019:2340392.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Tam E, Sung HK, Lam NH, You S, Cho S, Ahmed SM, et al. Role of Mitochondrial Iron Overload in Mediating Cell Death in H9c2 Cells. Cells. 2022;12.

  62. Villalpando-Rodriguez GE, Gibson SB. Reactive Oxygen Species (ROS) Regulates Different Types of Cell Death by Acting as a Rheostat. Oxid Med Cell Longev. 2021;2021:9912436.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Guo C, Sun L, Chen X, Zhang D. Oxidative stress, mitochondrial damage and neurodegenerative diseases. Neural Regen Res. 2013;8:2003–14.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. del Rey M, Benito R, Fontanillo C, Campos-Laborie FJ, Janusz K, Velasco-Hernandez T, et al. Deregulation of genes related to iron and mitochondrial metabolism in refractory anemia with ring sideroblasts. PLoS One. 2015;10:e0126555.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Roth M, Will B, Simkin G, Narayanagari S, Barreyro L, Bartholdy B, et al. Eltrombopag inhibits the proliferation of leukemia cells via reduction of intracellular iron and induction of differentiation. Blood. 2012;120:386–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Kuno S, Fujita H, Tanaka YK, Ogra Y, Iwai K. Iron-induced NCOA4 condensation regulates ferritin fate and iron homeostasis. EMBO Rep. 2022;23:e54278.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Zhu K, Lang Z, Zhan Y, Tao Q, Yu Z, Chen L, et al. A novel 10-gene ferroptosis-related prognostic signature in acute myeloid leukemia. Front Oncol. 2022;12:1023040.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Kao Y-R, Chen J, Kumari R, Tatiparthy M, Ma Y, Aivalioti MM, et al. Cytoplasmic labile iron accumulates in aging stem cells perturbing a key rheostat for identity control. bioRxiv. 2021;08.03.454947

  69. Rosenbloom KR, Sloan CA, Malladi VS, Dreszer TR, Learned K, Kirkup VM, et al. ENCODE data in the UCSC Genome Browser: year 5 update. Nucleic Acids Res. 2013;41:D56–63.

    Article  CAS  PubMed  Google Scholar 

  70. Rauluseviciute I, Riudavets-Puig R, Blanc-Mathieu R, Castro-Mondragon JA, Ferenc K, Kumar V, et al. JASPAR 2024: 20th anniversary of the open-access database of transcription factor binding profiles. Nucleic Acids Res. 2024;52:D174–D182.

    Article  PubMed  Google Scholar 

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Acknowledgements

The animal facilities of Jinan university are appreciative acknowledged. The skillful assistance in flow cytometry of Xianda Chen and Wanling You are gratefully acknowledged. We would like to thank the members of the Zhenyu Ju’s laboratory for useful suggestions and excellent technical support. We would like to thank Xingguo Liu, Feixiang Bao and Xudong Zhu for their great assistance in mitochondria-related experiments. This work was supported by the grants 92049112, 81901403, 32300663, 82230047 from the National Natural Science Foundation of China, grant 2021YFA1100103 from the National Basic Research Program of China, grant 2023KCXTD004 from Innovation Team Project of Universities in Guangdong Province, and grant 20204BCJ22027 supported by Jiangxi Provincial Natural Science Foundation.

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Author notes

  1. These authors contributed equally: Weiwei Yi, Jinhua Zhang, Yingxin Huang.

Authors and Affiliations

  1. Department of Cardiology, the First Affiliated Hospital of Jinan University, Guangzhou, 510630, Guangdong, China

    Weiwei Yi, Jinhua Zhang & Jun Guo

  2. Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou, 510632, Guangdong, China

    Weiwei Yi, Yingxin Huang, Qiang Zhan, Mi Zou, Zhenyu Ju & Zhiyang Chen

  3. Department of Hematology, Children’s Hospital, Capital Institute of Pediatrics, Beijing, 100020, China

    Xiang Cheng

  4. Mengniu Institute of Nutrition Science, Global R&D Innovation Center, Shanghai, China

    Xuguang Zhang

  5. Shanghai Institute of Nutrition and Health, The Chinese Academy of Sciences, Shanghai, China

    Xuguang Zhang

  6. Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Institute of Translational Medicine, Zhuhai People’s Hospital Affiliated with Jinan University, Jinan University, Zhuhai, 519000, Guangdong, China

    Zhinan Yin

  7. The Biomedical Translational Research Institute, Health Science Center (School of Medicine), Jinan University, Guangzhou, 510632, Guangdong, China

    Zhinan Yin

  8. Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China

    Si Tao

  9. State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300020, China

    Hui Cheng

  10. The Second Affiliated Hospital, School of Public Health, State Key Laboratory of Experimental Hematology, Zhejiang University School of Medicine, Hangzhou, 310058, Zhejiang, China

    Fudi Wang

  11. The First Affiliated Hospital, Basic Medical Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China

    Fudi Wang

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  1. Weiwei Yi
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Contributions

W Yi, Y Huang and J Zhang performed the majority of experiments and analyzed the data. Q Zhan analyzed the RNA-Seq data and performed WB assay. M Zou participated in samples collection and preparation. H Cheng, S Tao and X Cheng supervised the leukemic stem cell-related experiments. Z Yin, F Wang, X Zhang and J Guo revised the manuscript. Z Ju and Z Chen designed and supervised the study. Z Chen wrote the manuscript.

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Correspondence to Jun Guo, Zhenyu Ju or Zhiyang Chen.

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Yi, W., Zhang, J., Huang, Y. et al. Ferritin-mediated mitochondrial iron homeostasis is essential for the survival of hematopoietic stem cells and leukemic stem cells. Leukemia (2024). https://doi.org/10.1038/s41375-024-02169-y

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