Go to
JCI Insight
Citations to this article
Iléana Antony-Debré, … , Gregory M.K. Poon, Ulrich Steidl
Published October 30, 2017
Citation Information: J Clin Invest. 2017;127(12):4297-4313. https://doi.org/10.1172/JCI92504.
Citation Information: J Clin Invest. 2017;127(12):4297-4313. https://doi.org/10.1172/JCI92504.
Abstract
The transcription factor PU.1 is often impaired in patients with acute myeloid leukemia (AML). Here, we used AML cells that already had low PU.1 levels and further inhibited PU.1 using either RNA interference or, to our knowledge, first-in-class small-molecule inhibitors of PU.1 that we developed specifically to allosterically interfere with PU.1-chromatin binding through interaction with the DNA minor groove that flanks PU.1-binding motifs. These small molecules of the heterocyclic diamidine family disrupted the interaction of PU.1 with target gene promoters and led to downregulation of canonical PU.1 transcriptional targets. shRNA or small-molecule inhibition of PU.1 in AML cells from either PU.1lo mutant mice or human patients with AML-inhibited cell growth and clonogenicity and induced apoptosis. In murine and human AML (xeno)transplantation models, treatment with our PU.1 inhibitors decreased tumor burden and resulted in increased survival. Thus, our study provides proof of concept that PU.1 inhibition has potential as a therapeutic strategy for the treatment of AML and for the development of small-molecule inhibitors of PU.1.
Authors
Iléana Antony-Debré, Ananya Paul, Joana Leite, Kelly Mitchell, Hye Mi Kim, Luis A. Carvajal, Tihomira I. Todorova, Kenneth Huang, Arvind Kumar, Abdelbasset A. Farahat, Boris Bartholdy, Swathi-Rao Narayanagari, Jiahao Chen, Alberto Ambesi-Impiombato, Adolfo A. Ferrando, Ioannis Mantzaris, Evripidis Gavathiotis, Amit Verma, Britta Will, David W. Boykin, W. David Wilson, Gregory M.K. Poon, Ulrich Steidl
Total citations by year
Citation information
Citations to this article (71)
| Title and authors | Publication | Year |
|---|---|---|
|
Role of MMP9 High Expression Neutrophils in Neutrophil Extracellular Traps Formation and Myocardial Ischemia/Reperfusion Injury
Shiyu Hu, Feng Zhang, Jingpu Wang, Jian Zhang, Chenguang Li, Yang Lyu, Yiwen Wang, Rong Huang, Yang Gao, Hongbo Yang, Juying Qian, Wenwen Tang, Jiatian Cao, Junbo Ge |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) | 2025 |
|
Alternative Approach to Sequence-Specific Recognition of DNA: Cooperative Stacking of Dication Dimers—Sensitivity to Compound Curvature, Aromatic Structure, and DNA Sequence
Paul A, Terrell JR, Farahat AA, Ogbonna EN, Kumar A, Boykin DW, Neidle S, Wilson WD |
ACS Chemical Biology | 2025 |
|
PSPC1 exerts an oncogenic role in AML by regulating a leukemic transcription program in cooperation with PU.1.
Hong J, Sui P, Li Y, Xu KY, Lee JH, Wang J, Chen S, Zhang P, Wingate N, Noor A, Yuan Y, Hromas R, Zhou H, Hamamoto K, Su R, Yin CC, Ye F, Quesada AE, Chen J, Huang S, Zhou D, You MJ, Yang FC, Wang J, Xu M |
Cell stem cell | 2025 |
|
PU.1 induces tumor-associated macrophages promoting glioma progression through BTK-mediated Akt/mTOR pathway activation.
Song G, Zhang Z, Chen Y, Hou W, Zhong W, Zhou Y, Zhang A, Xu Y |
American journal of cancer research | 2024 |
|
Epigallocatechin gallate regulates the myeloid-specific transcription factor PU.1 in macrophages
Karpurapu M, Kakarala KK, Chung S, Nie Y, Koley A, Dougherty P, Christman JW |
PloS one | 2024 |
|
Induction of AML cell differentiation using HOXA9/DNA binding inhibitors as a potential therapeutic option for HOXA9‐dependent AML
Lambert M, Jambon S, Bouhlel MA, Depauw S, Vrevin J, Blanck S, Marot G, Figeac M, Preudhomme C, Quesnel B, Boykin DW, David\u2010Cordonnier M |
HemaSphere | 2024 |
|
Targeting transcription factor pu.1 for improving neurologic outcomes after spinal cord injury
Shi Y, Zheng M, Luo Y, Li J, Ouyang F, Zhao Y, Wang J, Ma Z, Meng C, Bi Y, Cheng L, Jing J |
Frontiers in Neuroscience | 2024 |
|
Pharmacological restriction of genomic binding sites redirects PU.1 pioneer transcription factor activity.
Taylor SJ, Stauber J, Bohorquez O, Tatsumi G, Kumari R, Chakraborty J, Bartholdy BA, Schwenger E, Sundaravel S, Farahat AA, Wheat JC, Goldfinger M, Verma A, Kumar A, Boykin DW, Stengel KR, Poon GMK, Steidl U |
Nature genetics | 2024 |
|
Single GC base pair recognition by a heterocyclic diamidine: structures, affinities, and dynamics.
Ogbonna EN, Terrell JR, Paul A, Farahat AA, Poon GMK, Boykin DW, Wilson WD |
RSC advances | 2024 |
|
Chemical restriction of PU.1 genomic binding sites activates alternate gene networks.
|
Nature genetics | 2024 |
|
Redistribution of PU.1 partner transcription factor RUNX1 binding secures cell survival during leukemogenesis.
Bender A, Boydere F, Jayavelu AK, Tibello A, König T, Aleth H, Meyer Zu Hörste G, Vogl T, Rosenbauer F |
The EMBO journal | 2024 |
|
Pharmacological blockade of a pioneer transcription factor
Cermakova K, Hodges HC |
Cancer research | 2024 |
|
Airway and parenchyma transcriptomics in a house dust mite model of experimental asthma
Tu X, Gomez HM, Kim RY, Brown AC, de Jong E, Galvao I, Faiz A, Bosco A, Horvat JC, Hansbro P, Donovan C |
Respiratory Research | 2023 |
|
Antagonistic action of GPS2 and KDM1A at enhancers governs alternative macrophage activation by interleukin 4
Huang Z, Efthymiadou A, Liang N, Fan R, Treuter E |
Nucleic Acids Research | 2023 |
|
SWI/SNF Blockade Disrupts PU.1-Directed Enhancer Programs in Normal Hematopoietic Cells and Acute Myeloid Leukemia
Chambers C, Cermakova K, Chan YS, Kurtz K, Wohlan K, Lewis AH, Wang C, Pham A, Dejmek M, Sala M, Loeza Cabrera M, Aguilar R, Nencka R, Lacorazza HD, Rau RE, Hodges HC |
Cancer research | 2023 |
|
Circular RNAs: pivotal role in the leukemogenesis and novel indicators for the diagnosis and prognosis of acute myeloid leukemia
Rahmati A, Mafi A, Soleymani F, Babaei Aghdam Z, Masihipour N, Ghezelbash B, Asemi R, Aschner M, Vakili O, Homayoonfal M, Asemi Z, Sharifi M, Azadi A, Mirzaei H, Aghadavod E |
Frontiers in Oncology | 2023 |
|
Analyses of Genes Critical to Tumor Survival Reveal Potential ‘Supertargets’: Focus on Transcription
Chetverina D, Vorobyeva NE, Gyorffy B, Shtil AA, Erokhin M |
Cancers | 2023 |
|
X-ray Structure Characterization of the Selective Recognition of AT Base Pair Sequences.
Ogbonna EN, Paul A, Farahat AA, Terrell JR, Mineva E, Ogbonna V, Boykin DW, Wilson WD |
2023 | |
|
The roles of ubiquitination in AML.
Wei Z, Su L, Gao S |
Annals of Hematology | 2023 |
|
Regeneration of the cerebral cortex by direct chemical reprogramming of macrophages into neuronal cells in acute ischemic stroke
Ninomiya I, Koyama A, Otsu Y, Onodera O, Kanazawa M |
Frontiers in cellular neuroscience | 2023 |
|
A novel molecular class that recruits HDAC/MECP2 complexes to PU.1 motifs reduces neuroinflammation
Ralvenius WT, Mungenast AE, Woolf H, Huston MM, Gillingham TZ, Godin SK, Penney J, Cam HP, Gao F, Fernandez CG, Czako B, Lightfoot Y, Ray WJ, Beckmann A, Goate AM, Marcora E, Romero-Molina C, Ayata P, Schaefer A, Gjoneska E, Tsai LH |
Journal of Experimental Medicine | 2023 |
|
DNA selection by the master transcription factor PU.1.
Terrell JR, Taylor SJ, Schneider AL, Lu Y, Vernon TN, Xhani S, Gumpper RH, Luo M, Wilson WD, Steidl U, Poon GMK |
Cell Reports | 2023 |
|
The Small-Molecule E26-Transformation-Specific Inhibitor TK216 Attenuates the Oncogenic Properties of Pediatric Leukemia.
Sharma R, Zhang C, Narendran A |
Genes & development | 2023 |
|
Transcription factors in the development and treatment of immune disorders
Patalano SD, Fuxman Bass P, Fuxman Bass JI |
Transcription | 2023 |
|
Neurofibromin and suppression of tumorigenesis: beyond the GAP
J Mo, S Moye, R McKay, L Le |
Oncogene | 2022 |
|
SPI1-induced downregulation of FTO promotes GBM progression by regulating pri-miR-10a processing in an m6A-dependent manner
S Zhang, S Zhao, Y Qi, B Li, H Wang, Z Pan, H Xue, C Jin, W Qiu, Z Chen, Q Guo, Y Fan, J Xu, Z Gao, S Wang, X Guo, L Deng, S Ni, F Xue, J Wang, R Zhao, G Li |
Molecular Therapy — Nucleic Acids | 2022 |
|
Transcription factor–nucleosome dynamics from plasma cfDNA identifies ER-driven states in breast cancer
Rao S, Han AL, Zukowski A, Kopin E, Sartorius CA, Kabos P, Ramachandran S |
Science Advances | 2022 |
|
Characterisation of the Circulating Transcriptomic Landscape in Inflammatory Bowel Disease Provides Evidence for Dysregulation of Multiple Transcription Factors Including NFE2, SPI1, CEBPB, and IRF2
Nowak JK, Adams AT, Kalla R, Lindstrøm JC, Vatn S, Bergemalm D, Keita ÅV, Gomollón F, Jahnsen J, Vatn MH, Ricanek P, Ostrowski J, Walkowiak J, Halfvarson J, Satsangi J |
Journal of Crohn's & colitis | 2022 |
|
Single-cell RNA sequencing uncovers the nuclear decoy lincRNA PIRAT as a regulator of systemic monocyte immunity during COVID-19.
Aznaourova M, Schmerer N, Janga H, Zhang Z, Pauck K, Bushe J, Volkers SM, Wendisch D, Georg P, Ntini E, Aillaud M, Gündisch M, Mack E, Skevaki C, Keller C, Bauer C, Bertrams W, Marsico A, Nist A, Stiewe T, Gruber AD, Ruppert C, Li Y, Garn H, Sander LE, Schmeck B, Schulte LN |
Proceedings of the National Academy of Sciences | 2022 |
|
PU.1 inhibition does not attenuate cardiac function deterioration or fibrosis in a murine model of myocardial infarction.
Nong Y, Guo Y, Ou Q, Gumpert A, Tomlin A, Zhu X, Bolli R |
Molecular and Cellular Biochemistry | 2022 |
|
Dissection of the MEF2D-IRF8 transcriptional circuit dependency in acute myeloid leukemia
Pingul BY, Huang H, Chen Q, Alikarami F, Zhang Z, Qi J, Bernt KM, Berger SL, Cao Z, Shi J |
iScience | 2022 |
|
Control of ribosomal RNA synthesis by hematopoietic transcription factors.
Antony C, George SS, Blum J, Somers P, Thorsheim CL, Wu-Corts DJ, Ai Y, Gao L, Lv K, Tremblay MG, Moss T, Tan K, Wilusz JE, Ganley ARD, Pimkin M, Paralkar VR |
Molecular Cell | 2022 |
|
PLK2 Single Nucleotide Variant in Gastric Cancer Patients Affects miR-23b-5p Binding.
Dominkuš PP, Mesic A, Hudler P |
Journal of Gastric Cancer | 2022 |
|
Drug Design and DNA Structural Research Inspired by the Neidle Laboratory: DNA Minor Groove Binding and Transcription Factor Inhibition by Thiophene Diamidines
Ogbonna EN, Paul A, Terrell JR, Fang Z, Chen C, Poon GM, Boykin DW, Wilson WD |
Bioorganic & Medicinal Chemistry | 2022 |
|
Cytokine responses to LPS in reprogrammed monocytes are associated with the transcription factor PU.1
Tuerxun K, Midtbö K, Särndahl E, Vorontsov E, Karlsson R, Persson A, Kruse R, Eklund D |
Journal of leukocyte biology | 2022 |
|
PU.1 promotes development of rheumatoid arthritis via repressing FLT3 in macrophages and fibroblast-like synoviocytes
Tu J, Chen W, Fang Y, Han D, Chen Y, Jiang H, Tan X, Xu Z, Wu X, Wang H, Zhu X, Hong W, Li Z, Zhu C, Wang X, Wei W |
Annals of the rheumatic diseases | 2022 |
|
Preleukemic and leukemic evolution at the stem cell level
J Stauber, JM Greally, U Steidl |
Blood | 2021 |
|
GSK-3: a multifaceted player in acute leukemias
AM Martelli, C Evangelisti, F Paganelli, F Chiarini, JA McCubrey |
Leukemia | 2021 |
|
Transcription Factors, R-Loops and Deubiquitinating Enzymes: Emerging Targets in Myelodysplastic Syndromes and Acute Myeloid Leukemia
SM Barabino, E Citterio, AE Ronchi |
Cancers | 2021 |
|
FcγR engagement reprograms neutrophils into antigen cross-presenting cells that elicit acquired anti-tumor immunity
V Mysore, X Cullere, J Mears, F Rosetti, K Okubo, PX Liew, F Zhang, I Madera-Salcedo, F Rosenbauer, RM Stone, JC Aster, UH von Andrian, AH Lichtman, S Raychaudhuri, TN Mayadas |
Nature Communications | 2021 |
|
Developing next generation immunomodulatory drugs and their combinations in multiple myeloma
A Thakurta, WE Pierceall, MD Amatangelo, E Flynt, A Agarwal |
Oncotarget | 2021 |
|
Engineered modular heterocyclic-diamidines for sequence-specific recognition of mixed AT/GC base pairs at the DNA minor groove
P Guo, A Farahat, A Paul, D Boykin, W Wilson |
Chemical Science | 2021 |
|
Transcriptional, Epigenetic and Metabolic Programming of Tumor-Associated Macrophages
I Larionova, E Kazakova, M Patysheva, J Kzhyshkowska |
Cancers | 2020 |
|
Therapeutic Vulnerabilities of Transcription Factors in AML
I Khan, E Eklund, A Gartel |
Molecular cancer therapeutics | 2020 |
|
Targeting Microglial Population Dynamics in Alzheimer’s Disease: Are We Ready for a Potential Impact on Immune Function?
M Martin-Estebane, D Gomez-Nicola |
Frontiers in cellular neuroscience | 2020 |
|
Small Sequence‐Sensitive Compounds for Specific Recognition of the G⋅C Base Pair in DNA Minor Groove
AA Farahat, P Guo, H Shoeib, A Paul, DW Boykin, WD Wilson |
Chemistry - A European Journal | 2020 |
|
Intrinsic disorder controls two functionally distinct dimers of the master transcription factor PU.1
S Xhani, S Lee, HM Kim, S Wang, S Esaki, VL Ha, M Khanezarrin, GL Fernandez, AV Albrecht, JM Aramini, MW Germann, GM Poon |
Science Advances | 2020 |
|
Extending the σ-Hole Motif for Sequence Specific Recognition of the DNA Minor Groove
P Guo, AA Farahat, A Paul, A Kumar, DW Boykin, WD Wilson |
Biochemistry | 2020 |
|
Dissecting Dynamic and Hydration Contributions to Sequence-Dependent DNA Minor Groove Recognition
VL Ha, N Erlitzki, AA Farahat, A Kumar, DW Boykin, GM Poon |
Biophysical Journal | 2020 |
|
Paradoxical Role of AT-rich Interactive Domain 1A in Restraining Pancreatic Carcinogenesis
S Ferri-Borgogno, S Barui, AM McGee, T Griffiths, PK Singh, CG Piett, B Ghosh, S Bhattacharyya, A Singhi, K Pradhan, A Verma, Z Nagel, A Maitra, S Gupta |
Cancers | 2020 |
|
Targeting transcriptional coregulator OCA-B/Pou2af1 blocks activated autoreactive T cells in the pancreas and type 1 diabetes
H Kim, J Perovanovic, A Shakya, Z Shen, CN German, A Ibarra, JL Jafek, NP Lin, BD Evavold, DH Chou, PE Jensen, X He, D Tantin |
Journal of Experimental Medicine | 2020 |
|
Recent Insights into the Involvement of Novel Transcription Factors, The Microbiome, and Dysregulated Cellular Metabolism in Pulmonary Fibrosis Pathogenesis
SC Rowan, S Bora, A Burman, T Xie, P Chen |
American journal of respiratory cell and molecular biology | 2019 |
|
Targeting transcription factors in cancer — from undruggable to reality
JH Bushweller |
Nature Reviews Cancer | 2019 |
|
PTEN Tumor-Suppressor: The Dam of Stemness in Cancer
F Luongo, F Colonna, F Calapà, S Vitale, ME Fiori, RD Maria |
Cancers | 2019 |
|
PRDM16s transforms megakaryocyte-erythroid progenitors into myeloid leukemia–initiating cells
T Hu, K Morita, MC Hill, Y Jiang, A Kitano, Y Saito, F Wang, X Mao, KA Hoegenauer, K Morishita, JF Martin, PA Futreal, K Takahashi, D Nakada |
Blood | 2019 |
|
Heterocyclic Diamidine DNA ligands as HOXA9 Transcription Factor Inhibitors: Design, Molecular Evaluation and Cellular Consequences in HOXA9-Dependant Leukemia Cell Model
S Depauw, M Lambert, S Jambon, A Paul, P Peixoto, R Nhili, L Marongiu, M Figeac, C Dassi, C Paul-Constant, B Billoré, A Kumar, AA Farahat, MA Ismail, E Mineva, DP Sweat, CE Stephens, DW Boykin, WD Wilson, MH David-Cordonnier |
Journal of Medicinal Chemistry | 2019 |
|
Recent developments in compounds acting in the DNA minor groove
A Rahman, P O'Sullivan, I Rozas |
MedChemComm | 2019 |
|
A New Generation of Minor-Groove-Binding—Heterocyclic Diamidines That Recognize G·C Base Pairs in an AT Sequence Context
A Paul, P Guo, D Boykin, W Wilson |
Molecules (Basel, Switzerland) | 2019 |
|
Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development
EV Rothenberg, H Hosokawa, J Ungerbäck |
Frontiers in immunology | 2019 |
|
Cohesin Members Stag1 and Stag2 Display Distinct Roles in Chromatin Accessibility and Topological Control of HSC Self-Renewal and Differentiation
AD Viny, RL Bowman, Y Liu, VP Lavallée, SE Eisman, W Xiao, BH Durham, A Navitski, J Park, S Braunstein, B Alija, A Karzai, IS Csete, M Witkin, E Azizi, T Baslan, CJ Ott, D Peer, J Dekker, R Koche, RL Levine |
Cell Stem Cell | 2019 |
|
Pro-inflammatory cytokine blockade attenuates myeloid expansion in a murine model of rheumatoid arthritis
G Hernandez, TS Mills, JL Rabe, JS Chavez, S Kuldanek, G Kirkpatrick, L Noetzli, WK Jubair, M Zanche, JR Myers, BM Stevens, CJ Fleenor, B Adane, CA Dinarello, J Ashton, CT Jordan, JD Paola, JR Hagman, VM Holers, KA Kuhn, EM Pietras |
Haematologica | 2019 |
|
Targeting PFKFB3 sensitizes chronic myelogenous leukemia cells to tyrosine kinase inhibitor
Y Zhu, L Lu, C Qiao, Y Shan, H Li, S Qian, M Hong, H Zhao, J Li, Z Yang, Y Chen |
Oncogene | 2018 |
|
Targeting Transcription Factors for Cancer Treatment
M Lambert, S Jambon, S Depauw, MH David-Cordonnier |
Molecules (Basel, Switzerland) | 2018 |
|
Targeting transcription factors in acute myeloid leukemia
H Takei, SS Kobayashi |
International Journal of Hematology | 2018 |
|
Bound Compound, Interfacial Water, and Phenyl Ring Rotation Dynamics of a Compound in the DNA Minor Groove
NK Harika, WD Wilson |
Biochemistry | 2018 |
|
An overview of recent advances in duplex DNA recognition by small molecules
S Bhaduri, N Ranjan, DP Arya |
Beilstein Journal of Organic Chemistry | 2018 |
|
Mapping interfacial hydration in ETS-family transcription factor complexes with DNA: a chimeric approach
AV Albrecht, HM Kim, GM Poon |
Nucleic Acids Research | 2018 |
|
Compound Shape Effects in Minor Groove Binding Affinity and Specificity for Mixed Sequence DNA
P Guo, AA Farahat, A Paul, NK Harika, DW Boykin, WD Wilson |
Journal of the American Chemical Society | 2018 |
|
T-ALL leukemia stem cell 'stemness' is epigenetically controlled by the master regulator SPI1
H Zhu, L Zhang, Y Wu, B Dong, W Guo, M Wang, L Yang, X Fan, Y Tang, N Liu, X Lei, H Wu |
eLife | 2018 |
|
First Structure of a Designed Minor Groove Binding Heterocyclic Cation that Specifically Recognizes Mixed DNA Base Pair Sequences
NK Harika, MW Germann, WD Wilson |
Chemistry - A European Journal | 2017 |
|
A modular design for minor groove binding and recognition of mixed base pair sequences of DNA
P Guo, A Paul, A Kumar, NK Harika, S Wang, AA Farahat, DW Boykin, WD Wilson |
Chemical Communications | 2017 |
Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)