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Current Molecular Pharmacology

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ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

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Research Article

A Deeply Quiescent Subset of CML LSC depend on FAO yet Avoid Deleterious ROS by Suppressing Mitochondrial Complex I

Author(s): Nyam-Osor Chimge, Min-Hsuan Chen, Cu Nguyen, Yuqi Zhao, Xiwei Wu, Paulina Garcia Gonzalez, Heather Ogana, Samantha Hurwitz, Jia-Ling Teo, Xiaolong Chen, Juan Du, Victor Jin, Yong-Mi Kim, Masaya Ono, Rafael J. Argüello and Michael Kahn*

Volume 17, 2024

Published on: 02 October, 2023

Article ID: e060923220758 Pages: 19

DOI: 10.2174/1874467217666230906092236

Price: $65

Abstract

Background and Objective: Disease relapse and therapy resistance remain serious impediments to treating cancer. Leukemia stem cells (LSC) are therapy resistant and the cause of relapse. A state of deep quiescence appears to enable cancer stem cells (CSC) to acquire new somatic mutations essential for disease progression and therapy resistance. Both normal hematopoietic stem cells (HSC) and LSC share many common features, thereby complicating the safe elimination of LSC. A recent study demonstrated that long lived normal oocytes exist without mitochondrial complex I (MC-1), expressing it in a developmentally regulated fashion, thereby mitigating their vulnerability to ROS. Quiescent CSC rely on mitochondrial FAO, without complex I expression, thereby avoiding the generation of damaging ROS, similar to long lived normal human stem cells. A deeper understanding of the biology of therapy resistance is important for the development of optimal strategies to attain complete leukemia cures.

Methods: Here, using scRNA-sequencing and ATAC-seq on primary chronic myelogenous leukemia (CML) patient samples, combined with bioinformatics analyses, we further examine the heterogeneity of a previously characterized in vitro imatinib-selected CD34-CD38- CML LSC population. We utilized a series of functional analyses, including single-cell metabolomic and Seahorse analyses, to validate the existence of the deepest quiescent leukemia initiators (LI) subset.

Results: Current study revealed heterogeneity of therapy resistant LSC in CML patients and their existence of two functionally distinct states. The most deeply quiescent LI suppress the expression of MC-1, yet are highly dependent on fatty acid oxidation (FAO) for their metabolic requirements and ATAC-seq demonstrated increased chromatin accessibility in this population, all consistent with an extremely primitive, quiescent stemness transcriptional signature. Importantly, the specific CREB binding protein (CBP)/β-catenin antagonist ICG-001 initiates the differentiation of LSC, including LI, decreases chromatin accessibility with differentiation and increasing expression of MC-1, CD34, CD38 and BCR-ABL1, thereby resensitizing them to imatinib.

Conclusion: We investigated the biological aspects related to LSC heterogeneity in CML patients and demonstrated the ability of specific small molecule CBP/β-catenin antagonists to safely eliminate deeply quiescent therapy resistant CSC. These observations may represent an attractive generalizable therapeutic strategy that could help develop better protocols to eradicate the quiescent LSC population.

[1]
Giles, F.J.; DeAngelo, D.J.; Baccarani, M.; Deininger, M.; Guilhot, F.; Hughes, T.; Mauro, M.; Radich, J.; Ottmann, O.; Cortes, J. Optimizing outcomes for patients with advanced disease in chronic myelogenous leukemia. Semin. Oncol., 2008, 35(1), S1-S17.
[http://dx.doi.org/10.1053/j.seminoncol.2007.12.002] [PMID: 18346528]
[2]
Mahon, F.X.; Réa, D.; Guilhot, J.; Guilhot, F.; Huguet, F.; Nicolini, F.; Legros, L.; Charbonnier, A.; Guerci, A.; Varet, B.; Etienne, G.; Reiffers, J.; Rousselot, P. Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: The prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol., 2010, 11(11), 1029-1035.
[http://dx.doi.org/10.1016/S1470-2045(10)70233-3] [PMID: 20965785]
[3]
Ross, D.M.; Branford, S.; Seymour, J.F.; Schwarer, A.P.; Arthur, C.; Yeung, D.T.; Dang, P.; Goyne, J.M.; Slader, C.; Filshie, R.J.; Mills, A.K.; Melo, J.V.; White, D.L.; Grigg, A.P.; Hughes, T.P. Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: Results from the TWISTER study. Blood, 2013, 122(4), 515-522.
[http://dx.doi.org/10.1182/blood-2013-02-483750] [PMID: 23704092]
[4]
Saussele, S.; Richter, J.; Guilhot, J.; Gruber, F.X.; Hjorth-Hansen, H.; Almeida, A.; Janssen, J.J.W.M.; Mayer, J.; Koskenvesa, P.; Panayiotidis, P.; Olsson-Strömberg, U.; Martinez-Lopez, J.; Rousselot, P.; Vestergaard, H.; Ehrencrona, H.; Kairisto, V.; Machová Poláková, K.; Müller, M.C.; Mustjoki, S.; Berger, M.G.; Fabarius, A.; Hofmann, W.K.; Hochhaus, A.; Pfirrmann, M.; Mahon, F.X.; Ossenkoppele, G.; Pagoni, M.N.; Söderlund, S.; Escoffre-Barbe, M.; Etienne, G.; Dengler, J.; Huguet, F.; von Bubnoff, N.; Klamova, H.; Faber, E.; Guilhot, F.; Lotfi, K.; Rea, D.; Brümmendorf, T.H.; de Greef, G.E.; Stenke, L.; Nicolini, F.E.; Legros, L.; Burchert, A.; Voglova, J.; Charbonnier, A.; Gyan, E.; Kunzmann, V.; Westerweel, P.E. Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI): A prespecified interim analysis of a prospective, multicentre, non-randomised, trial. Lancet Oncol., 2018, 19(6), 747-757.
[http://dx.doi.org/10.1016/S1470-2045(18)30192-X] [PMID: 29735299]
[5]
Shah, N.P.; García-Gutiérrez, V.; Jiménez-Velasco, A.; Larson, S.; Saussele, S.; Rea, D.; Mahon, F.X.; Levy, M.Y.; Gómez-Casares, M.T.; Pane, F.; Nicolini, F.E.; Mauro, M.J.; Sy, O.; Martin-Regueira, P.; Lipton, J.H. Dasatinib discontinuation in patients with chronic-phase chronic myeloid leukemia and stable deep molecular response: The DASFREE study. Leuk. Lymphoma, 2020, 61(3), 650-659.
[http://dx.doi.org/10.1080/10428194.2019.1675879] [PMID: 31647335]
[6]
Holyoake, T.L.; Vetrie, D. The chronic myeloid leukemia stem cell: Stemming the tide of persistence. Blood, 2017, 129(12), 1595-1606.
[http://dx.doi.org/10.1182/blood-2016-09-696013] [PMID: 28159740]
[7]
Bolton-Gillespie, E.; Schemionek, M.; Klein, H.U.; Flis, S.; Hoser, G.; Lange, T.; Nieborowska-Skorska, M.; Maier, J.; Kerstiens, L.; Koptyra, M.; Müller, M.C.; Modi, H.; Stoklosa, T.; Seferynska, I.; Bhatia, R.; Holyoake, T.L.; Koschmieder, S.; Skorski, T. Genomic instability may originate from imatinib-refractory chronic myeloid leukemia stem cells. Blood, 2013, 121(20), 4175-4183.
[http://dx.doi.org/10.1182/blood-2012-11-466938] [PMID: 23543457]
[8]
Vetrie, D.; Helgason, G.V.; Copland, M. The leukaemia stem cell: Similarities, differences and clinical prospects in CML and AML. Nat. Rev. Cancer, 2020, 20(3), 158-173.
[http://dx.doi.org/10.1038/s41568-019-0230-9] [PMID: 31907378]
[9]
Jamieson, C.H.M.; Ailles, L.E.; Dylla, S.J.; Muijtjens, M.; Jones, C.; Zehnder, J.L.; Gotlib, J.; Li, K.; Manz, M.G.; Keating, A.; Sawyers, C.L.; Weissman, I.L. Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. N. Engl. J. Med., 2004, 351(7), 657-667.
[http://dx.doi.org/10.1056/NEJMoa040258] [PMID: 15306667]
[10]
Lemoli, R.M.; Salvestrini, V.; Bianchi, E.; Bertolini, F.; Fogli, M.; Amabile, M.; Tafuri, A.; Salati, S.; Zini, R.; Testoni, N.; Rabascio, C.; Rossi, L.; Martin-Padura, I.; Castagnetti, F.; Marighetti, P.; Martinelli, G.; Baccarani, M.; Ferrari, S.; Manfredini, R. Molecular and functional analysis of the stem cell compartment of chronic myelogenous leukemia reveals the presence of a CD34- cell population with intrinsic resistance to imatinib. Blood, 2009, 114(25), 5191-5200.
[http://dx.doi.org/10.1182/blood-2008-08-176016] [PMID: 19855080]
[11]
Ng, S.W.K.; Mitchell, A.; Kennedy, J.A.; Chen, W.C.; McLeod, J.; Ibrahimova, N.; Arruda, A.; Popescu, A.; Gupta, V.; Schimmer, A.D.; Schuh, A.C.; Yee, K.W.; Bullinger, L.; Herold, T.; Görlich, D.; Büchner, T.; Hiddemann, W.; Berdel, W.E.; Wörmann, B.; Cheok, M.; Preudhomme, C.; Dombret, H.; Metzeler, K.; Buske, C.; Löwenberg, B.; Valk, P.J.M.; Zandstra, P.W.; Minden, M.D.; Dick, J.E.; Wang, J.C.Y. A 17-gene stemness score for rapid determination of risk in acute leukaemia. Nature, 2016, 540(7633), 433-437.
[http://dx.doi.org/10.1038/nature20598] [PMID: 27926740]
[12]
Quek, L.; Otto, G.W.; Garnett, C.; Lhermitte, L.; Karamitros, D.; Stoilova, B.; Lau, I.J.; Doondeea, J.; Usukhbayar, B.; Kennedy, A.; Metzner, M.; Goardon, N.; Ivey, A.; Allen, C.; Gale, R.; Davies, B.; Sternberg, A.; Killick, S.; Hunter, H.; Cahalin, P.; Price, A.; Carr, A.; Griffiths, M.; Virgo, P.; Mackinnon, S.; Grimwade, D.; Freeman, S.; Russell, N.; Craddock, C.; Mead, A.; Peniket, A.; Porcher, C.; Vyas, P. Genetically distinct leukemic stem cells in human CD34- acute myeloid leukemia are arrested at a hemopoietic precursor-like stage. J. Exp. Med., 2016, 213(8), 1513-1535.
[http://dx.doi.org/10.1084/jem.20151775] [PMID: 27377587]
[13]
Taussig, D.C.; Vargaftig, J.; Miraki-Moud, F.; Griessinger, E.; Sharrock, K.; Luke, T.; Lillington, D.; Oakervee, H.; Cavenagh, J.; Agrawal, S.G.; Lister, T.A.; Gribben, J.G.; Bonnet, D. Leukemia-initiating cells from some acute myeloid leukemia patients with mutated nucleophosmin reside in the CD34- fraction. Blood, 2010, 115(10), 1976-1984.
[http://dx.doi.org/10.1182/blood-2009-02-206565] [PMID: 20053758]
[14]
Zhao, Y.; Wu, K.; Wu, Y.; Melendez, E.; Smbatyan, G.; Massiello, D.; Kahn, M. Characterization of imatinib resistant CML leukemic stem/initiating cells and their sensitivity to CBP/catenin antagonists. Curr. Mol. Pharmacol., 2018, 11(2), 113-121.
[http://dx.doi.org/10.2174/1874467210666170919155739] [PMID: 28933312]
[15]
Zhao, Y.; Masiello, D.; McMillian, M.; Nguyen, C.; Wu, Y.; Melendez, E.; Smbatyan, G.; Kida, A.; He, Y.; Teo, J-L.; Kahn, M. CBP/catenin antagonist safely eliminates drug-resistant leukemia-initiating cells. Oncogene, 2016, 35(28), 3705-3717.
[http://dx.doi.org/10.1038/onc.2015.438] [PMID: 26657156]
[16]
Giustacchini, A.; Thongjuea, S.; Barkas, N.; Woll, P.S.; Povinelli, B.J.; Booth, C.A.G.; Sopp, P.; Norfo, R.; Rodriguez-Meira, A.; Ashley, N.; Jamieson, L.; Vyas, P.; Anderson, K.; Segerstolpe, Å.; Qian, H.; Olsson-Strömberg, U.; Mustjoki, S.; Sandberg, R.; Jacobsen, S.E.W.; Mead, A.J. Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia. Nat. Med., 2017, 23(6), 692-702.
[http://dx.doi.org/10.1038/nm.4336] [PMID: 28504724]
[17]
Warfvinge, R.; Geironson, L.; Sommarin, M.N.E.; Lang, S.; Karlsson, C.; Roschupkina, T.; Stenke, L.; Stentoft, J.; Olsson-Strömberg, U.; Hjorth-Hansen, H.; Mustjoki, S.; Soneji, S.; Richter, J.; Karlsson, G. Single-cell molecular analysis defines therapy response and immunophenotype of stem cell subpopulations in CML. Blood, 2017, 129(17), 2384-2394.
[http://dx.doi.org/10.1182/blood-2016-07-728873] [PMID: 28122740]
[18]
Vallette, F.M.; Olivier, C.; Lézot, F.; Oliver, L.; Cochonneau, D.; Lalier, L.; Cartron, P.F.; Heymann, D. Dormant, quiescent, tolerant and persister cells: Four synonyms for the same target in cancer. Biochem. Pharmacol., 2019, 162, 169-176.
[http://dx.doi.org/10.1016/j.bcp.2018.11.004] [PMID: 30414937]
[19]
Oren, Y.; Tsabar, M.; Cuoco, M.S.; Amir-Zilberstein, L.; Cabanos, H.F.; Hütter, J.C.; Hu, B.; Thakore, P.I.; Tabaka, M.; Fulco, C.P.; Colgan, W.; Cuevas, B.M.; Hurvitz, S.A.; Slamon, D.J.; Deik, A.; Pierce, K.A.; Clish, C.; Hata, A.N.; Zaganjor, E.; Lahav, G.; Politi, K.; Brugge, J.S.; Regev, A. Cycling cancer persister cells arise from lineages with distinct programs. Nature, 2021, 596(7873), 576-582.
[http://dx.doi.org/10.1038/s41586-021-03796-6] [PMID: 34381210]
[20]
Ito, K.; Ito, K. Leukemia stem cells as a potential target to achieve therapy-free remission in chronic myeloid leukemia. Cancers, 2021, 13(22), 5822.
[http://dx.doi.org/10.3390/cancers13225822] [PMID: 34830976]
[21]
Zhang, B.; Ho, Y.W.; Huang, Q.; Maeda, T.; Lin, A.; Lee, S.; Hair, A.; Holyoake, T.L.; Huettner, C.; Bhatia, R. Altered microenvironmental regulation of leukemic and normal stem cells in chronic myelogenous leukemia. Cancer Cell, 2012, 21(4), 577-592.
[http://dx.doi.org/10.1016/j.ccr.2012.02.018] [PMID: 22516264]
[22]
Zhao, C.; Blum, J.; Chen, A.; Kwon, H.Y.; Jung, S.H.; Cook, J.M.; Lagoo, A.; Reya, T. Loss of beta-catenin impairs the renewal of normal and CML stem cells in vivo. Cancer Cell, 2007, 12(6), 528-541.
[http://dx.doi.org/10.1016/j.ccr.2007.11.003] [PMID: 18068630]
[23]
Ito, K.; Carracedo, A.; Weiss, D.; Arai, F.; Ala, U.; Avigan, D.E.; Schafer, Z.T.; Evans, R.M.; Suda, T.; Lee, C.H.; Pandolfi, P.P. A PML-PPAR-δ pathway for fatty acid oxidation regulates hematopoietic stem cell maintenance. Nat. Med., 2012, 18(9), 1350-1358.
[http://dx.doi.org/10.1038/nm.2882] [PMID: 22902876]
[24]
Pernes, G.; Flynn, M.C.; Lancaster, G.I.; Murphy, A.J. Fat for fuel: Lipid metabolism in haematopoiesis. Clin. Transl. Immunol., 2019, 8(12), e1098.
[http://dx.doi.org/10.1002/cti2.1098] [PMID: 31890207]
[25]
Warr, M.R.; Binnewies, M.; Flach, J.; Reynaud, D.; Garg, T.; Malhotra, R.; Debnath, J.; Passegué, E. FOXO3A directs a protective autophagy program in haematopoietic stem cells. Nature, 2013, 494(7437), 323-327.
[http://dx.doi.org/10.1038/nature11895] [PMID: 23389440]
[26]
Rodríguez-Nuevo, A.; Torres-Sanchez, A.; Duran, J.M.; De Guirior, C.; Martínez-Zamora, M.A.; Böke, E. Oocytes maintain ROS-free mitochondrial metabolism by suppressing complex I. Nature, 2022, 607(7920), 756-761.
[http://dx.doi.org/10.1038/s41586-022-04979-5] [PMID: 35859172]
[27]
Stuart, T.; Butler, A.; Hoffman, P.; Hafemeister, C.; Papalexi, E.; Mauck, W.M., III; Hao, Y.; Stoeckius, M.; Smibert, P.; Satija, R. Comprehensive integration of single-cell data. Cell, 2019, 177(7), 1888-1902.e21.
[http://dx.doi.org/10.1016/j.cell.2019.05.031] [PMID: 31178118]
[28]
Wagner, A.; Wang, C.; Fessler, J.; DeTomaso, D.; Avila-Pacheco, J.; Kaminski, J.; Zaghouani, S.; Christian, E.; Thakore, P.; Schellhaass, B.; Akama-Garren, E.; Pierce, K.; Singh, V.; Ron-Harel, N.; Douglas, V.P.; Bod, L.; Schnell, A.; Puleston, D.; Sobel, R.A.; Haigis, M.; Pearce, E.L.; Soleimani, M.; Clish, C.; Regev, A.; Kuchroo, V.K.; Yosef, N. Metabolic modeling of single Th17 cells reveals regulators of autoimmunity. Cell, 2021, 184(16), 4168-4185.e21.
[http://dx.doi.org/10.1016/j.cell.2021.05.045] [PMID: 34216539]
[29]
Argüello, R.J.; Combes, A.J.; Char, R.; Gigan, J.P.; Baaziz, A.I.; Bousiquot, E.; Camosseto, V.; Samad, B.; Tsui, J.; Yan, P.; Boissonneau, S.; Figarella-Branger, D.; Gatti, E.; Tabouret, E.; Krummel, M.F.; Pierre, P. SCENITH: A flow cytometry-based method to functionally profile energy metabolism with single-cell resolution. Cell Metab., 2020, 32(6), 1063-1075.e7.
[http://dx.doi.org/10.1016/j.cmet.2020.11.007] [PMID: 33264598]
[30]
Hu, X.; Ono, M.; Chimge, N.O.; Chosa, K.; Nguyen, C.; Melendez, E.; Lou, C.H.; Lim, P.; Termini, J.; Lai, K.K.Y.; Fueger, P.T.; Teo, J.L.; Higuchi, Y.; Kahn, M. Differential Kat3 usage orchestrates the integration of cellular metabolism with differentiation. Cancers, 2021, 13(23), 5884.
[http://dx.doi.org/10.3390/cancers13235884] [PMID: 34884992]
[31]
Lai, K.K.Y.; Hu, X.; Chosa, K.; Nguyen, C.; Lin, D.P.; Lai, K.K.; Kato, N.; Higuchi, Y.; Highlander, S.K.; Melendez, E.; Eriguchi, Y.; Fueger, P.T.; Ouellette, A.J.; Chimge, N.O.; Ono, M.; Kahn, M. p300 Serine 89: A critical signaling integrator and its effects on intestinal homeostasis and repair. Cancers, 2021, 13(6), 1288.
[http://dx.doi.org/10.3390/cancers13061288] [PMID: 33799418]
[32]
Ono, M.; Shitashige, M.; Honda, K.; Isobe, T.; Kuwabara, H.; Matsuzuki, H.; Hirohashi, S.; Yamada, T. Label-free quantitative proteomics using large peptide data sets generated by nanoflow liquid chromatography and mass spectrometry. Mol. Cell. Proteomics, 2006, 5(7), 1338-1347.
[http://dx.doi.org/10.1074/mcp.T500039-MCP200] [PMID: 16552026]
[33]
Ono, M.; Lai, K.K.Y.; Wu, K.; Nguyen, C.; Lin, D.P.; Murali, R.; Kahn, M. Nuclear receptor/Wnt beta-catenin interactions are regulated via differential CBP/p300 coactivator usage. PLoS One, 2018, 13(7), e0200714.
[http://dx.doi.org/10.1371/journal.pone.0200714] [PMID: 30020971]
[34]
Lindqvist, L.M.; Tandoc, K.; Topisirovic, I.; Furic, L. Cross-talk between protein synthesis, energy metabolism and autophagy in cancer. Curr. Opin. Genet. Dev., 2018, 48, 104-111.
[http://dx.doi.org/10.1016/j.gde.2017.11.003] [PMID: 29179096]
[35]
Kohli, L.; Passegué, E. Surviving change: The metabolic journey of hematopoietic stem cells. Trends Cell Biol., 2014, 24(8), 479-487.
[http://dx.doi.org/10.1016/j.tcb.2014.04.001] [PMID: 24768033]
[36]
Carracedo, A.; Cantley, L.C.; Pandolfi, P.P. Cancer metabolism: Fatty acid oxidation in the limelight. Nat. Rev. Cancer, 2013, 13(4), 227-232.
[http://dx.doi.org/10.1038/nrc3483] [PMID: 23446547]
[37]
Thomas, P.D.; Kahn, M. Kat3 coactivators in somatic stem cells and cancer stem cells: Biological roles, evolution, and pharmacologic manipulation. Cell Biol. Toxicol., 2016, 32(1), 61-81.
[http://dx.doi.org/10.1007/s10565-016-9318-0] [PMID: 27008332]
[38]
Kumari, A.; Brendel, C.; Hochhaus, A.; Neubauer, A.; Burchert, A. Low BCR-ABL expression levels in hematopoietic precursor cells enable persistence of chronic myeloid leukemia under imatinib. Blood, 2012, 119(2), 530-539.
[http://dx.doi.org/10.1182/blood-2010-08-303495] [PMID: 22101898]
[39]
Cumbo, C.; Anelli, L.; Specchia, G.; Albano, F. Monitoring of Minimal Residual Disease (MRD) in chronic myeloid leukemia: Recent advances. Cancer Manag. Res., 2020, 12, 3175-3189.
[http://dx.doi.org/10.2147/CMAR.S232752] [PMID: 32440215]
[40]
Gang, E.J.; Hsieh, Y-T.; Pham, J.; Zhao, Y.; Nguyen, C.; Huantes, S.; Park, E.; Naing, K.; Klemm, L.; Swaminathan, S.; Conway, E.M.; Pelus, L.M.; Crispino, J.; Mullighan, C.G.; McMillan, M.; Müschen, M.; Kahn, M.; Kim, Y-M. Small-molecule inhibition of CBP/catenin interactions eliminates drug-resistant clones in acute lymphoblastic leukemia. Oncogene, 2014, 33(17), 2169-2178.
[http://dx.doi.org/10.1038/onc.2013.169] [PMID: 23728349]
[41]
Kim, Y.M.; Gang, E.J.; Kahn, M. CBP/Catenin antagonists: Targeting LSCs’ achilles heel. Exp. Hematol., 2017, 52, 1-11.
[http://dx.doi.org/10.1016/j.exphem.2017.04.010] [PMID: 28479420]
[42]
Duchartre, Y.; Kim, Y.M.; Kahn, M. The Wnt signaling pathway in cancer. Crit. Rev. Oncol. Hematol., 2016, 99, 141-149.
[http://dx.doi.org/10.1016/j.critrevonc.2015.12.005] [PMID: 26775730]
[43]
Ranzoni, A.M.; Tangherloni, A.; Berest, I.; Riva, S.G.; Myers, B.; Strzelecka, P.M.; Xu, J.; Panada, E.; Mohorianu, I.; Zaugg, J.B.; Cvejic, A. Integrative single-cell RNA-seq and ATAC-seq analysis of human developmental hematopoiesis. Cell Stem Cell, 2021, 28(3), 472-487.e7.
[http://dx.doi.org/10.1016/j.stem.2020.11.015] [PMID: 33352111]
[44]
Bricambert, J.; Miranda, J.; Benhamed, F.; Girard, J.; Postic, C.; Dentin, R. Salt-inducible kinase 2 links transcriptional coactivator p300 phosphorylation to the prevention of ChREBP-dependent hepatic steatosis in mice. J. Clin. Invest., 2010, 120(12), 4316-4331.
[http://dx.doi.org/10.1172/JCI41624] [PMID: 21084751]
[45]
Liu, Y.; Dentin, R.; Chen, D.; Hedrick, S.; Ravnskjaer, K.; Schenk, S.; Milne, J.; Meyers, D.J.; Cole, P.; Iii, J.Y.; Olefsky, J.; Guarente, L.; Montminy, M. A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange. Nature, 2008, 456(7219), 269-273.
[http://dx.doi.org/10.1038/nature07349] [PMID: 18849969]
[46]
Kahn, M. Taking the road less traveled - the therapeutic potential of CBP/β-catenin antagonists. Expert Opin. Ther. Targets, 2021, 25(9), 701-719.
[http://dx.doi.org/10.1080/14728222.2021.1992386] [PMID: 34633266]
[47]
Belser, M.; Walker, D.W. Role of prohibitins in aging and therapeutic potential against age-related diseases. Front. Genet., 2021, 12, 714228.
[http://dx.doi.org/10.3389/fgene.2021.714228] [PMID: 34868199]
[48]
Gurevich, I.; Flores, A.M.; Aneskievich, B.J. Corepressors of agonist-bound nuclear receptors. Toxicol. Appl. Pharmacol., 2007, 223(3), 288-298.
[http://dx.doi.org/10.1016/j.taap.2007.05.019] [PMID: 17628626]
[49]
Ren, L.; Meng, L.; Gao, J.; Lu, M.; Guo, C.; Li, Y.; Rong, Z.; Ye, Y. PHB2 promotes colorectal cancer cell proliferation and tumorigenesis through NDUFS1-mediated oxidative phosphorylation. Cell Death Dis., 2023, 14(1), 44.
[http://dx.doi.org/10.1038/s41419-023-05575-9] [PMID: 36658121]
[50]
Chu, S.; McDonald, T.; Lin, A.; Chakraborty, S.; Huang, Q.; Snyder, D.S.; Bhatia, R. Persistence of leukemia stem cells in chronic myelogenous leukemia patients in prolonged remission with imatinib treatment. Blood, 2011, 118(20), 5565-5572.
[http://dx.doi.org/10.1182/blood-2010-12-327437] [PMID: 21931114]
[51]
Ross, D.M.; Branford, S.; Seymour, J.F.; Schwarer, A.P.; Arthur, C.; Bartley, P.A.; Slader, C.; Field, C.; Dang, P.; Filshie, R.J.; Mills, A.K.; Grigg, A.P.; Melo, J.V.; Hughes, T.P. Patients with chronic myeloid leukemia who maintain a complete molecular response after stopping imatinib treatment have evidence of persistent leukemia by DNA PCR. Leukemia, 2010, 24(10), 1719-1724.
[http://dx.doi.org/10.1038/leu.2010.185] [PMID: 20811403]
[52]
Saleh, T.; Gewirtz, D.A. Considering therapy-induced senescence as a mechanism of tumour dormancy contributing to disease recurrence. Br. J. Cancer, 2022, 126(10), 1363-1365.
[http://dx.doi.org/10.1038/s41416-022-01787-6] [PMID: 35304605]
[53]
Agudo, J.; Park, E.S.; Rose, S.A.; Alibo, E.; Sweeney, R.; Dhainaut, M.; Kobayashi, K.S.; Sachidanandam, R.; Baccarini, A.; Merad, M.; Brown, B.D. Quiescent tissue stem cells evade immune surveillance. Immunity, 2018, 48(2), 271-285.e5.
[http://dx.doi.org/10.1016/j.immuni.2018.02.001] [PMID: 29466757]
[54]
Rehman, S.K.; Haynes, J.; Collignon, E.; Brown, K.R.; Wang, Y.; Nixon, A.M.L.; Bruce, J.P.; Wintersinger, J.A.; Singh Mer, A.; Lo, E.B.L.; Leung, C.; Lima-Fernandes, E.; Pedley, N.M.; Soares, F.; McGibbon, S.; He, H.H.; Pollet, A.; Pugh, T.J.; Haibe-Kains, B.; Morris, Q.; Ramalho-Santos, M.; Goyal, S.; Moffat, J.; O’Brien, C.A. Colorectal cancer cells enter a diapause-like DTP state to survive chemotherapy. Cell, 2021, 184(1), 226-242.e21.
[http://dx.doi.org/10.1016/j.cell.2020.11.018] [PMID: 33417860]
[55]
Bonnet, D. Normal and leukemic CD34-negative human hematopoietic stem cells. Rev. Clin. Exp. Hematol., 2001, 5(1), 42-61.
[http://dx.doi.org/10.1046/j.1468-0734.2001.00028.x] [PMID: 11486732]
[56]
Zanjani, E.D.; Almeida-Porada, G.; Livingston, A.G.; Zeng, H.; Ogawa, M. Reversible expression of CD34 by adult human bone marrow long-term engrafting hematopoietic stem cells. Exp. Hematol., 2003, 31(5), 406-412.
[http://dx.doi.org/10.1016/S0301-472X(03)00051-1] [PMID: 12763139]
[57]
Lemoli, R.M.; Bertolini, F.; Petrucci, M.T.; Gregorj, C.; Ricciardi, M.R.; Fogli, M.; Curti, A.; Rabascio, C.; Pandolfi, S.; Ferrari, S.; Fo, R.; Baccarani, M.; Tafuri, A. Functional and kinetic characterization of granulocyte colony-stimulating factor-primed CD34 − human stem cells. Br. J. Haematol., 2003, 123(4), 720-729.
[http://dx.doi.org/10.1046/j.1365-2141.2003.04673.x] [PMID: 14616978]
[58]
Rodgers, J.T.; King, K.Y.; Brett, J.O.; Cromie, M.J.; Charville, G.W.; Maguire, K.K.; Brunson, C.; Mastey, N.; Liu, L.; Tsai, C.R.; Goodell, M.A.; Rando, T.A. mTORC1 controls the adaptive transition of quiescent stem cells from G0 to GAlert. Nature, 2014, 510(7505), 393-396.
[http://dx.doi.org/10.1038/nature13255] [PMID: 24870234]
[59]
Cuesta-Mateos, C.; Terrón, F.; Herling, M. CCR7 in blood cancers - Review of its pathophysiological roles and the potential as a therapeutic target. Front. Oncol., 2021, 11, 736758.
[http://dx.doi.org/10.3389/fonc.2021.736758] [PMID: 34778050]
[60]
Bührer, E.D.; Amrein, M.A.; Forster, S.; Isringhausen, S.; Schürch, C.M.; Bhate, S.S.; Brodie, T.; Zindel, J.; Stroka, D.; Sayed, M.A.; Nombela-Arrieta, C.; Radpour, R.; Riether, C.; Ochsenbein, A.F. Splenic red pulp macrophages provide a niche for CML stem cells and induce therapy resistance. Leukemia, 2022, 36(11), 2634-2646.
[http://dx.doi.org/10.1038/s41375-022-01682-2] [PMID: 36163264]
[61]
Li, Z.; Ma, R.; Ma, S.; Tian, L.; Lu, T.; Zhang, J.; Mundy-Bosse, B.L.; Zhang, B.; Marcucci, G.; Caligiuri, M.A.; Yu, J. ILC1s control leukemia stem cell fate and limit development of AML. Nat. Immunol., 2022, 23(5), 718-730.
[http://dx.doi.org/10.1038/s41590-022-01198-y] [PMID: 35487987]
[62]
Heidel, F.H.; Bullinger, L.; Feng, Z.; Wang, Z.; Neff, T.A.; Stein, L.; Kalaitzidis, D.; Lane, S.W.; Armstrong, S.A. Genetic and pharmacologic inhibition of β-catenin targets imatinib-resistant leukemia stem cells in CML. Cell Stem Cell, 2012, 10(4), 412-424.
[http://dx.doi.org/10.1016/j.stem.2012.02.017] [PMID: 22482506]
[63]
Hecht, A.; Vleminckx, K.; Stemmler, M.P.; van Roy, F.; Kemler, R. The p300/CBP acetyltransferases function as transcriptional coactivators of beta-catenin in vertebrates. EMBO J., 2000, 19(8), 1839-1850.
[http://dx.doi.org/10.1093/emboj/19.8.1839] [PMID: 10775268]
[64]
Takemaru, K.I.; Moon, R.T. The transcriptional coactivator CBP interacts with beta-catenin to activate gene expression. J. Cell Biol., 2000, 149(2), 249-254.
[http://dx.doi.org/10.1083/jcb.149.2.249] [PMID: 10769018]
[65]
Teo, J.L.; Kahn, M. The Wnt signaling pathway in cellular proliferation and differentiation: A tale of two coactivators. Adv. Drug Deliv. Rev., 2010, 62(12), 1149-1155.
[http://dx.doi.org/10.1016/j.addr.2010.09.012] [PMID: 20920541]
[66]
Creyghton, M.P.; Cheng, A.W.; Welstead, G.G.; Kooistra, T.; Carey, B.W.; Steine, E.J.; Hanna, J.; Lodato, M.A.; Frampton, G.M.; Sharp, P.A.; Boyer, L.A.; Young, R.A.; Jaenisch, R. Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc. Natl. Acad. Sci., 2010, 107(50), 21931-21936.
[http://dx.doi.org/10.1073/pnas.1016071107] [PMID: 21106759]
[67]
Hnisz, D.; Abraham, B.J.; Lee, T.I.; Lau, A.; Saint-André, V.; Sigova, A.A.; Hoke, H.A.; Young, R.A. Super-enhancers in the control of cell identity and disease. Cell, 2013, 155(4), 934-947.
[http://dx.doi.org/10.1016/j.cell.2013.09.053] [PMID: 24119843]
[68]
Martire, S.; Nguyen, J.; Sundaresan, A.; Banaszynski, L.A. Differential contribution of p300 and CBP to regulatory element acetylation in mESCs. BMC Mol. Cell Biol., 2020, 21(1), 55.
[http://dx.doi.org/10.1186/s12860-020-00296-9] [PMID: 32690000]
[69]
Mirzadeh Azad, F.; Atlasi, Y. WNT-regulated transcriptional enhancers and stem cell plasticity. Trends Cell Biol., 2021, 31(7), 525-528.
[http://dx.doi.org/10.1016/j.tcb.2021.03.007] [PMID: 33775538]
[70]
Zamudio, A.V.; Dall’Agnese, A.; Henninger, J.E.; Manteiga, J.C.; Afeyan, L.K.; Hannett, N.M.; Coffey, E.L.; Li, C.H.; Oksuz, O.; Sabari, B.R.; Boija, A.; Klein, I.A.; Hawken, S.W.; Spille, J.H.; Decker, T.M.; Cisse, I.I.; Abraham, B.J.; Lee, T.I.; Taatjes, D.J.; Schuijers, J.; Young, R.A. Mediator condensates localize signaling factors to key cell identity genes. Mol. Cell, 2019, 76(5), 753-766.e6.
[http://dx.doi.org/10.1016/j.molcel.2019.08.016] [PMID: 31563432]
[71]
Vo, N.; Goodman, R.H. CREB-binding protein and p300 in transcriptional regulation. J. Biol. Chem., 2001, 276(17), 13505-13508.
[http://dx.doi.org/10.1074/jbc.R000025200] [PMID: 11279224]
[72]
Chan, W.I.; Hannah, R.L.; Dawson, M.A.; Pridans, C.; Foster, D.; Joshi, A.; Göttgens, B.; Van Deursen, J.M.; Huntly, B.J.P. The transcriptional coactivator Cbp regulates self-renewal and differentiation in adult hematopoietic stem cells. Mol. Cell. Biol., 2011, 31(24), 5046-5060.
[http://dx.doi.org/10.1128/MCB.05830-11] [PMID: 22006020]
[73]
Kawasaki, H.; Eckner, R.; Yao, T.P.; Taira, K.; Chiu, R.; Livingston, D.M.; Yokoyama, K.K. Distinct roles of the co-activators p300 and CBP in retinoic-acid-induced F9-cell differentiation. Nature, 1998, 393(6682), 284-289.
[http://dx.doi.org/10.1038/30538] [PMID: 9607768]
[74]
Rebel, V.I.; Kung, A.L.; Tanner, E.A.; Yang, H.; Bronson, R.T.; Livingston, D.M. Distinct roles for CREB-binding protein and p300 in hematopoietic stem cell self-renewal. Proc. Natl. Acad. Sci., 2002, 99(23), 14789-14794.
[http://dx.doi.org/10.1073/pnas.232568499] [PMID: 12397173]
[75]
Teo, J.L.; Ma, H.; Nguyen, C.; Lam, C.; Kahn, M. Specific inhibition of CBP/β-catenin interaction rescues defects in neuronal differentiation caused by a presenilin-1 mutation. Proc. Natl. Acad. Sci., 2005, 102(34), 12171-12176.
[http://dx.doi.org/10.1073/pnas.0504600102] [PMID: 16093313]
[76]
Yang, K.; Wang, F.; Zhang, H.; Wang, X.; Chen, L.; Su, X.; Wu, X.; Han, Q.; Chen, Z.; Chen, Z.S.; Fu, L. Target inhibition of CBP induced cell senescence in BCR-ABL- T315I mutant chronic myeloid leukemia. Front. Oncol., 2021, 10, 588641.
[http://dx.doi.org/10.3389/fonc.2020.588641] [PMID: 33585207]
[77]
Zhang, Y.; Wang, S.; Kang, W.; Liu, C.; Dong, Y.; Ren, F.; Wang, Y.; Zhang, J.; Wang, G.; To, K.F.; Zhang, X.; Sung, J.J.Y.; Chang, Z.; Yu, J. CREPT facilitates colorectal cancer growth through inducing Wnt/β-catenin pathway by enhancing p300-mediated β-catenin acetylation. Oncogene, 2018, 37(26), 3485-3500.
[http://dx.doi.org/10.1038/s41388-018-0161-z] [PMID: 29563608]
[78]
Zimmer, S.N.; Zhou, Q.; Zhou, T.; Cheng, Z.; Abboud-Werner, S.L.; Horn, D.; Lecocke, M.; White, R.; Krivtsov, A.V.; Armstrong, S.A.; Kung, A.L.; Livingston, D.M.; Rebel, V.I. Crebbp haploinsufficiency in mice alters the bone marrow microenvironment, leading to loss of stem cells and excessive myelopoiesis. Blood, 2011, 118(1), 69-79.
[http://dx.doi.org/10.1182/blood-2010-09-307942] [PMID: 21555743]
[79]
Bavelloni, A.; Piazzi, M.; Raffini, M.; Faenza, I.; Blalock, W.L. Prohibitin 2: At a communications crossroads. IUBMB Life, 2015, 67(4), 239-254.
[http://dx.doi.org/10.1002/iub.1366] [PMID: 25904163]
[80]
Radich, J.P.; Dai, H.; Mao, M.; Oehler, V.; Schelter, J.; Druker, B.; Sawyers, C.; Shah, N.; Stock, W.; Willman, C.L.; Friend, S.; Linsley, P.S. Gene expression changes associated with progression and response in chronic myeloid leukemia. Proc. Natl. Acad. Sci., 2006, 103(8), 2794-2799.
[http://dx.doi.org/10.1073/pnas.0510423103] [PMID: 16477019]
[81]
Grassi, S.; Palumbo, S.; Mariotti, V.; Liberati, D.; Guerrini, F.; Ciabatti, E.; Salehzadeh, S.; Baratè, C.; Balducci, S.; Ricci, F.; Buda, G.; Iovino, L.; Mazziotta, F.; Ghio, F.; Ercolano, G.; Di Paolo, A.; Cecchettini, A.; Baldini, C.; Mattii, L.; Pellegrini, S.; Petrini, M.; Galimberti, S. The WNT pathway is relevant for the BCR-ABL1-independent resistance in chronic myeloid leukemia. Front. Oncol., 2019, 9, 532.
[http://dx.doi.org/10.3389/fonc.2019.00532] [PMID: 31293972]
[82]
Taskesen, E.; Staal, F.J.T.; Reinders, M.J.T. An integrated approach of gene expression and DNA-methylation profiles of WNT signaling genes uncovers novel prognostic markers in Acute Myeloid Leukemia. BMC Bioinform., 2015, 16(S4), S4.
[http://dx.doi.org/10.1186/1471-2105-16-S4-S4] [PMID: 25734857]
[83]
Ysebaert, L.; Chicanne, G.; Demur, C.; De Toni, F.; Prade-Houdellier, N.; Ruidavets, J-B.; Mansat-De Mas, V.; Rigal-Huguet, F.; Laurent, G.; Payrastre, B.; Manenti, S.; Racaud-Sultan, C. Expression of β-catenin by acute myeloid leukemia cells predicts enhanced clonogenic capacities and poor prognosis. Leukemia, 2006, 20(7), 1211-1216.
[http://dx.doi.org/10.1038/sj.leu.2404239] [PMID: 16688229]
[84]
Mikesch, J-H.; Steffen, B.; Berdel, W.E.; Serve, H.; Müller-Tidow, C. The emerging role of Wnt signaling in the pathogenesis of acute myeloid leukemia. Leukemia, 2007, 21(8), 1638-1647.
[http://dx.doi.org/10.1038/sj.leu.2404732] [PMID: 17554387]
[85]
Emami, K.H.; Nguyen, C.; Ma, H.; Kim, D.H.; Jeong, K.W.; Eguchi, M.; Moon, R.T.; Teo, J.L.; Kim, H.Y.; Moon, S.H.; Ha, J.R.; Kahn, M. A small molecule inhibitor of beta-catenin/CREB-binding protein transcription. Proc. Natl. Acad. Sci., 2004, 101(34), 12682-12687.
[http://dx.doi.org/10.1073/pnas.0404875101] [PMID: 15314234]
[86]
Lukaszewicz, A.I.; Nguyen, C.; Melendez, E.; Lin, D.P.; Teo, J.L.; Lai, K.K.Y.; Huttner, W.B.; Shi, S.H.; Kahn, M. The mode of stem cell division is dependent on the differential interaction of β-Catenin with the Kat3 coactivators CBP or p300. Cancers, 2019, 11(7), 962.
[http://dx.doi.org/10.3390/cancers11070962] [PMID: 31324005]
[87]
Manegold, P.; Lai, K.; Wu, Y.; Teo, J.L.; Lenz, H.J.; Genyk, Y.; Pandol, S.; Wu, K.; Lin, D.; Chen, Y.; Nguyen, C.; Zhao, Y.; Kahn, M. Differentiation therapy targeting the β-Catenin/CBP interaction in pancreatic cancer. Cancers, 2018, 10(4), 95.
[http://dx.doi.org/10.3390/cancers10040095] [PMID: 29596326]

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