{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T20:11:34Z","timestamp":1773259894715,"version":"3.50.1"},"reference-count":128,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T00:00:00Z","timestamp":1642032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Education, University and Research - Dipartimenti di Eccellenza","award":["L. 232\/2016"],"award-info":[{"award-number":["L. 232\/2016"]}]},{"DOI":"10.13039\/501100004271","name":"Sapienza University of Rome","doi-asserted-by":"publisher","award":["RP11916B88BC2710"],"award-info":[{"award-number":["RP11916B88BC2710"]}],"id":[{"id":"10.13039\/501100004271","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acute lymphoblastic leukaemia (ALL) is an aggressive haematological tumour driven by the malignant transformation and expansion of B-cell (B-ALL) or T-cell (T-ALL) progenitors. The evolution of T-ALL pathogenesis encompasses different master developmental pathways, including the main role played by Notch in cell fate choices during tissue differentiation. Recently, a growing body of evidence has highlighted epigenetic changes, particularly the altered expression of microRNAs (miRNAs), as a critical molecular mechanism to sustain T-ALL. The immune response is emerging as key factor in the complex multistep process of cancer but the role of miRNAs in anti-leukaemia response remains elusive. In this review we analyse the available literature on miRNAs as tuners of the immune response in T-ALL, focusing on their role in Natural Killer, T, T-regulatory and Myeloid-derived suppressor cells. A better understanding of this molecular crosstalk may provide the basis for the development of potential immunotherapeutic strategies in the leukemia field.<\/jats:p>","DOI":"10.3390\/ijms23020829","type":"journal-article","created":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T10:57:37Z","timestamp":1642071457000},"page":"829","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["MicroRNAs as Modulators of the Immune Response in T-Cell Acute Lymphoblastic Leukemia"],"prefix":"10.3390","volume":"23","author":[{"given":"Martina","family":"Del Gaizo","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University of Rome, 00161 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilaria","family":"Sergio","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University of Rome, 00161 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Lazzari","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University of Rome, 00161 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha","family":"Cialfi","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University of Rome, 00161 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Pelullo","sequence":"additional","affiliation":[{"name":"Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabella","family":"Screpanti","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Sapienza University of Rome, 00161 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5765-2611","authenticated-orcid":false,"given":"Maria Pia","family":"Felli","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University of Rome, 00161 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Jia, Y., and Wei, Y. (2020). Modulators of MicroRNA Function in the Immune System. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072357"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/nrm3838","article-title":"Regulation of microRNA biogenesis","volume":"15","author":"Ha","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/imr.12062","article-title":"RNA regulation of the immune system","volume":"253","author":"Ansel","year":"2013","journal-title":"Immunol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1093\/carcin\/bgp272","article-title":"Inflammation and cancer: Interweaving microRNA, free radical, cytokine and p53 pathways","volume":"31","author":"Schetter","year":"2010","journal-title":"Carcinogenesis"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/imr.12050","article-title":"MicroRNAs play a central role in molecular dysfunctions linking inflammation with cancer","volume":"253","author":"Tili","year":"2013","journal-title":"Immunol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"13944","DOI":"10.1073\/pnas.0506654102","article-title":"miR-15 and miR-16 induce apoptosis by targeting BCL2","volume":"102","author":"Cimmino","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.humimm.2020.10.009","article-title":"Myeloid-derived suppressor cells and regulatory T cells share common immunoregulatory pathways-related microRNAs that are dysregulated by acute lymphoblastic leukemia and chemotherapy","volume":"82","author":"Salem","year":"2021","journal-title":"Hum. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4350","DOI":"10.7150\/jca.35205","article-title":"MicroRNA networks regulate the differentiation, expansion and suppression function of myeloid-derived suppressor cells in tumor microenvironment","volume":"10","author":"Su","year":"2019","journal-title":"J. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1080\/10428190802626632","article-title":"Activation of miR-17-92 by NK-like homeodomain proteins suppresses apoptosis via reduction of E2F1 in T-cell acute lymphoblastic leukemia","volume":"50","author":"Nagel","year":"2009","journal-title":"Leuk Lymphoma"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4832","DOI":"10.4049\/jimmunol.1402248","article-title":"Responsiveness of Developing T Cells to IL-7 Signals Is Sustained by miR-17 approximately 92","volume":"195","author":"Regelin","year":"2015","journal-title":"J. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.coph.2009.05.003","article-title":"microRNAs and the immune response","volume":"9","author":"Tsitsiou","year":"2009","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.molimm.2020.05.002","article-title":"Regulation of CD4(+)CD25(+)FOXP3(+) cells in Pediatric Acute Lymphoblastic Leukemia (ALL): Implication of cytokines and miRNAs","volume":"124","author":"Elshal","year":"2020","journal-title":"Mol. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1182\/blood-2014-12-618892","article-title":"Dicer1 imparts essential survival cues in Notch-driven T-ALL via miR-21-mediated tumor suppressor Pdcd4 repression","volume":"126","author":"Junker","year":"2015","journal-title":"Blood"},{"key":"ref_14","first-page":"145","article-title":"The role of microRNAs in the control and mechanism of action of IL-10","volume":"380","author":"Quinn","year":"2014","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1038\/leu.2017.80","article-title":"Regulation of PI3K signaling in T-cell acute lymphoblastic leukemia: A novel PTEN\/Ikaros\/miR-26b mechanism reveals a critical targetable role for PIK3CD","volume":"31","author":"Yuan","year":"2017","journal-title":"Leukemia"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1007\/s12017-014-8335-5","article-title":"miR26a modulates Th17\/T reg balance in the EAE model of multiple sclerosis by targeting IL6","volume":"17","author":"Zhang","year":"2015","journal-title":"Neuromolecular Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1158\/0008-5472.CAN-12-2184","article-title":"RNA trafficking by acute myelogenous leukemia exosomes","volume":"73","author":"Huan","year":"2013","journal-title":"Cancer Res."},{"key":"ref_18","first-page":"2394","article-title":"Impact of microRNA-29b on natural killer cells in T-cell acute lymphoblastic leukemia","volume":"18","author":"Jin","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1038\/leu.2012.87","article-title":"Natural killer cell immune escape in acute myeloid leukemia","volume":"26","author":"Lion","year":"2012","journal-title":"Leukemia"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1111\/cas.12766","article-title":"Potential roles of microRNA-29a in the molecular pathophysiology of T-cell acute lymphoblastic leukemia","volume":"106","author":"Oliveira","year":"2015","journal-title":"Cancer Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"34288","DOI":"10.18632\/oncotarget.9103","article-title":"Identification of miR-34a-target interactions by a combined network based and experimental approach","volume":"7","author":"Hart","year":"2016","journal-title":"Oncotarget"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/s41419-018-1295-1","article-title":"miR-34a: A new player in the regulation of T cell function by modulation of NF-kappaB signaling","volume":"10","author":"Hart","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1182\/blood-2016-07-730614","article-title":"MUC1-mediated induction of myeloid-derived suppressor cells in patients with acute myeloid leukemia","volume":"129","author":"Pyzer","year":"2017","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1615\/CritRevImmunol.2013006858","article-title":"MicroRNA regulation of T-lymphocyte immunity: Modulation of molecular networks responsible for T-cell activation, differentiation, and development","volume":"33","author":"Podshivalova","year":"2013","journal-title":"Crit. Rev. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/leu.2011.273","article-title":"An oncogenic role of miR-142-3p in human T-cell acute lymphoblastic leukemia (T-ALL) by targeting glucocorticoid receptor-alpha and cAMP\/PKA pathways","volume":"26","author":"Lv","year":"2012","journal-title":"Leukemia"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"31894","DOI":"10.1038\/srep31894","article-title":"MiR-146b negatively regulates migration and delays progression of T-cell acute lymphoblastic leukemia","volume":"6","author":"Correia","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7053","DOI":"10.1182\/blood-2010-12-326629","article-title":"Modulation of microRNA expression in human T-cell development: Targeting of NOTCH3 by miR-150","volume":"117","author":"Ghisi","year":"2011","journal-title":"Blood"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.molimm.2018.07.022","article-title":"MicroRNA regulation of natural killer cell development and function in leukemia","volume":"115","author":"Saultz","year":"2019","journal-title":"Mol. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.15252\/embj.201489589","article-title":"Induced miR-99a expression represses Mtor cooperatively with miR-150 to promote regulatory T-cell differentiation","volume":"34","author":"Warth","year":"2015","journal-title":"EMBO J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.4049\/jimmunol.1301309","article-title":"MicroRNA-155 and MicroRNA-21 promote the expansion of functional myeloid-derived suppressor cells","volume":"192","author":"Li","year":"2014","journal-title":"J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3232061","DOI":"10.1155\/2020\/3232061","article-title":"The Role of MicroRNAs in Regulatory T Cells","volume":"2020","author":"Liu","year":"2020","journal-title":"J. Immunol. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.immuni.2010.09.009","article-title":"MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development","volume":"33","author":"Kahn","year":"2010","journal-title":"Immunity"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1126\/science.1141229","article-title":"Regulation of the germinal center response by microRNA-155","volume":"316","author":"Thai","year":"2007","journal-title":"Science"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3478","DOI":"10.1182\/blood-2011-12-398099","article-title":"miR-155 regulates IFN-gamma production in natural killer cells","volume":"119","author":"Trotta","year":"2012","journal-title":"Blood"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.immuni.2007.10.009","article-title":"microRNA-155 regulates the generation of immunoglobulin class-switched plasma cells","volume":"27","author":"Vigorito","year":"2007","journal-title":"Immunity"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Yao, R., Ma, Y.L., Liang, W., Li, H.H., Ma, Z.J., Yu, X., and Liao, Y.H. (2012). MicroRNA-155 modulates Treg and Th17 cells differentiation and Th17 cell function by targeting SOCS1. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0046082"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6171","DOI":"10.4049\/jimmunol.1100835","article-title":"Cutting edge: microRNA-181 promotes human NK cell development by regulating Notch signaling","volume":"187","author":"Cichocki","year":"2011","journal-title":"J. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.gene.2017.07.052","article-title":"MicroRNA-181a and its target Smad 7 as potential biomarkers for tracking child acute lymphoblastic leukemia","volume":"628","author":"Nabhan","year":"2017","journal-title":"Gene"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"7901","DOI":"10.1038\/s41598-017-08148-x","article-title":"Comprehensive miRNA expression profiling in human T-cell acute lymphoblastic leukemia by small RNA-sequencing","volume":"7","author":"Wallaert","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1111\/cas.12370","article-title":"Effect of microRNA-210 on prognosis and response to chemotherapeutic drugs in pediatric acute lymphoblastic leukemia","volume":"105","author":"Mei","year":"2014","journal-title":"Cancer Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3771","DOI":"10.1158\/0008-5472.CAN-15-0405","article-title":"Tumor-Promoting Effects of Myeloid-Derived Suppressor Cells Are Potentiated by Hypoxia-Induced Expression of miR-210","volume":"75","author":"Noman","year":"2015","journal-title":"Cancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1073\/pnas.86.6.2031","article-title":"Chromosomal translocation in a human leukemic stem-cell line disrupts the T-cell antigen receptor delta-chain diversity region and results in a previously unreported fusion transcript","volume":"86","author":"Begley","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2324","DOI":"10.1038\/leu.2014.133","article-title":"Notch and NF-kB signaling pathways regulate miR-223\/FBXW7 axis in T-cell acute lymphoblastic leukemia","volume":"28","author":"Kumar","year":"2014","journal-title":"Leukemia"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1158\/0008-5472.CAN-19-1471","article-title":"ARRB1-Promoted NOTCH1 Degradation Is Suppressed by OncomiR miR-223 in T-cell Acute Lymphoblastic Leukemia","volume":"80","author":"Shu","year":"2020","journal-title":"Cancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5445","DOI":"10.18632\/oncotarget.23539","article-title":"MicroRNA expression and activity in T-cell acute lymphoblastic leukemia","volume":"9","author":"Ye","year":"2018","journal-title":"Oncotarget"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"631","DOI":"10.3892\/etm.2021.10063","article-title":"MicroRNA-325 inhibits the proliferation and induces the apoptosis of T cell acute lymphoblastic leukemia cells in a BAG2-dependent manner","volume":"21","author":"Wang","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1007\/s11596-014-1330-0","article-title":"Detection of microvesicle miRNA expression in ALL subtypes and analysis of their functional roles","volume":"34","author":"Li","year":"2014","journal-title":"J. Huazhong Univ. Sci. Technol. Med. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"9993","DOI":"10.1038\/srep09993","article-title":"MicroRNA transcriptomes of distinct human NK cell populations identify miR-362-5p as an essential regulator of NK cell function","volume":"5","author":"Ni","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/ng.858","article-title":"A cooperative microRNA-tumor suppressor gene network in acute T-cell lymphoblastic leukemia (T-ALL)","volume":"43","author":"Mavrakis","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.3324\/haematol.2012.080432","article-title":"Clinico-biological features of 5202 patients with acute lymphoblastic leukemia enrolled in the Italian AIEOP and GIMEMA protocols and stratified in age cohorts","volume":"98","author":"Chiaretti","year":"2013","journal-title":"Haematologica"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/nrg3272","article-title":"The Notch signalling system: Recent insights into the complexity of a conserved pathway","volume":"13","author":"Guruharsha","year":"2012","journal-title":"Nat. Rev. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-3-319-89512-3_1","article-title":"Introduction to Molecular Mechanisms in Notch Signal Transduction and Disease Pathogenesis","volume":"1066","author":"Giaimo","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"613557","DOI":"10.3389\/fcell.2020.613557","article-title":"A Dynamic Role of Mastermind-Like 1: A Journey Through the Main (Path)ways Between Development and Cancer","volume":"8","author":"Zema","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/978-3-030-36422-9_10","article-title":"Molecular Mechanisms of Notch Signaling in Lymphoid Cell Lineages Development: NF-kappaB and Beyond","volume":"1227","author":"Tsaouli","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"R316","DOI":"10.1016\/j.cub.2010.02.018","article-title":"Thymocyte selection: Chemokine signaling is not only about the destination","volume":"20","author":"Gleimer","year":"2010","journal-title":"Curr. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1093\/intimm\/11.7.1017","article-title":"Expression pattern of notch1, 2 and 3 and Jagged1 and 2 in lymphoid and stromal thymus components: Distinct ligand-receptor interactions in intrathymic T cell development","volume":"11","author":"Felli","year":"1999","journal-title":"Int. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.smim.2010.04.015","article-title":"Notch regulation of early thymocyte development","volume":"22","author":"Ohtani","year":"2010","journal-title":"Semin. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1158\/1535-7163.MCT-18-0706","article-title":"Antileukemia Effects of Notch-Mediated Inhibition of Oncogenic PLK1 in B-Cell Acute Lymphoblastic Leukemia","volume":"18","author":"Kannan","year":"2019","journal-title":"Mol. Cancer Ther."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1182\/blood-2016-10-706465","article-title":"The genetics and molecular biology of T-ALL","volume":"129","author":"Girardi","year":"2017","journal-title":"Blood"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3337","DOI":"10.1093\/emboj\/19.13.3337","article-title":"Constitutive activation of NF-kappaB and T-cell leukemia\/lymphoma in Notch3 transgenic mice","volume":"19","author":"Bellavia","year":"2000","journal-title":"EMBO J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"S205","DOI":"10.3816\/CLM.2009.s.013","article-title":"Therapeutic targeting of NOTCH1 signaling in T-cell acute lymphoblastic leukemia","volume":"9","author":"Palomero","year":"2009","journal-title":"Clin. Lymphoma Myeloma"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"5601396","DOI":"10.1155\/2019\/5601396","article-title":"Notch\/CXCR4 Partnership in Acute Lymphoblastic Leukemia Progression","volume":"2019","author":"Tsaouli","year":"2019","journal-title":"J. Immunol. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1038\/nrc.2016.63","article-title":"The genetics and mechanisms of T cell acute lymphoblastic leukaemia","volume":"16","author":"Belver","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"6077","DOI":"10.1038\/onc.2016.133","article-title":"Characterization of activating mutations of NOTCH3 in T-cell acute lymphoblastic leukemia and anti-leukemic activity of NOTCH3 inhibitory antibodies","volume":"35","author":"Hu","year":"2016","journal-title":"Oncogene"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Zhdanovskaya, N., Firrincieli, M., Lazzari, S., Pace, E., Rossi, P.S., Felli, M.P., Talora, C., Screpanti, I., and Palermo, R. (2021). Targeting Notch to Maximize Chemotherapeutic Benefits: Rationale, Advanced Strategies, and Future Perspectives. Cancers, 13.","DOI":"10.3390\/cancers13205106"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.3389\/fimmu.2018.02165","article-title":"Notch and NF-kappaB: Coach and Players of Regulatory T-Cell Response in Cancer","volume":"9","author":"Ferrandino","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Pastorczak, A., Domka, K., Fidyt, K., Poprzeczko, M., and Firczuk, M. (2021). Mechanisms of Immune Evasion in Acute Lymphoblastic Leukemia. Cancers, 13.","DOI":"10.3390\/cancers13071536"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13045-020-01014-w","article-title":"NK cell-based cancer immunotherapy: From basic biology to clinical development","volume":"14","author":"Liu","year":"2021","journal-title":"J. Hematol. Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1159\/000365632","article-title":"Human natural killer cells: Origin, receptors, function, and clinical applications","volume":"164","author":"Moretta","year":"2014","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Valenzuela-Vazquez, L., Nunez-Enriquez, J.C., Sanchez-Herrera, J., Jimenez-Hernandez, E., Martin-Trejo, J.A., Espinoza-Hernandez, L.E., Medina-Sanson, A., Flores-Villegas, L.V., Penaloza-Gonzalez, J.G., and Refugio Torres-Nava, J. (2020). Functional characterization of NK cells in Mexican pediatric patients with acute lymphoblastic leukemia: Report from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0227314"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1182\/blood.2020009871","article-title":"Activated natural killer cells predict poor clinical prognosis in high-risk B- and T-cell acute lymphoblastic leukemia","volume":"138","author":"Duault","year":"2021","journal-title":"Blood"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1158\/2326-6066.CIR-16-0296","article-title":"Ex Vivo Expanded Adaptive NK Cells Effectively Kill Primary Acute Lymphoblastic Leukemia Cells","volume":"5","author":"Liu","year":"2017","journal-title":"Cancer Immunol. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3389\/fcell.2020.00017","article-title":"T Cell Dysfunction and Exhaustion in Cancer","volume":"8","author":"Zhang","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"5531","DOI":"10.21873\/anticanres.13746","article-title":"Expression of Immune Checkpoint Receptors on T-Cells and Their Ligands on Leukemia Blasts in Childhood Acute Leukemia","volume":"39","author":"Kang","year":"2019","journal-title":"Anticancer. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.prp.2018.10.021","article-title":"Expression and significance of CD47, PD1 and PDL1 in T-cell acute lymphoblastic lymphoma\/leukemia","volume":"215","author":"Yang","year":"2019","journal-title":"Pathol. Res. Pract."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2463","DOI":"10.1182\/blood.2019004547","article-title":"Single-cell RNA-seq reveals developmental plasticity with coexisting oncogenic states and immune evasion programs in ETP-ALL","volume":"137","author":"Anand","year":"2021","journal-title":"Blood"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Bayon-Calderon, F., Toribio, M.L., and Gonzalez-Garcia, S. (2020). Facts and Challenges in Immunotherapy for T-Cell Acute Lymphoblastic Leukemia. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207685"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"ra88","DOI":"10.1126\/scisignal.aaf2797","article-title":"AML suppresses hematopoiesis by releasing exosomes that contain microRNAs targeting c-MYB","volume":"9","author":"Hornick","year":"2016","journal-title":"Sci. Signal"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3297","DOI":"10.1182\/blood-2014-12-618470","article-title":"Characterization of CLL exosomes reveals a distinct microRNA signature and enhanced secretion by activation of BCR signaling","volume":"125","author":"Yeh","year":"2015","journal-title":"Blood"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1111\/j.1349-7006.2010.01624.x","article-title":"Distribution of Th17 cells and FoxP3(+) regulatory T cells in tumor-infiltrating lymphocytes, tumor-draining lymph nodes and peripheral blood lymphocytes in patients with gastric cancer","volume":"101","author":"Maruyama","year":"2010","journal-title":"Cancer Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"541","DOI":"10.3389\/fimmu.2020.00541","article-title":"NF-kappaB1 Regulates Immune Environment and Outcome of Notch-Dependent T-Cell Acute Lymphoblastic Leukemia","volume":"11","author":"Grazioli","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"4028","DOI":"10.4049\/jimmunol.1501291","article-title":"Adaptive Immunity to Leukemia Is Inhibited by Cross-Reactive Induced Regulatory T Cells","volume":"195","author":"Manlove","year":"2015","journal-title":"J. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2816498","DOI":"10.1155\/2019\/2816498","article-title":"CD4(+)CD25(high)CD127(low\/-)FoxP3 (+) Regulatory T-Cell Population in Acute Leukemias: A Review of the Literature","volume":"2019","author":"Niedzwiecki","year":"2019","journal-title":"J. Immunol. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.3389\/fimmu.2018.01288","article-title":"Notch Signaling in Myeloid Cells as a Regulator of Tumor Immune Responses","volume":"9","author":"Hossain","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"14839","DOI":"10.1038\/s41598-020-71810-4","article-title":"NOTCH3 signaling is essential for NF-kappaB activation in TLR-activated macrophages","volume":"10","author":"Monsalve","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"4645","DOI":"10.1242\/dev.02070","article-title":"MicroPrimer: The biogenesis and function of microRNA","volume":"132","author":"Du","year":"2005","journal-title":"Development"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3016","DOI":"10.1101\/gad.1262504","article-title":"The Drosha-DGCR8 complex in primary microRNA processing","volume":"18","author":"Han","year":"2004","journal-title":"Genes Dev."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3011","DOI":"10.1101\/gad.1158803","article-title":"Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs","volume":"17","author":"Yi","year":"2003","journal-title":"Genes Dev."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"402","DOI":"10.3389\/fendo.2018.00402","article-title":"Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation","volume":"9","author":"Hayder","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1080\/17460441.2020.1765770","article-title":"Challenges identifying efficacious miRNA therapeutics for cancer","volume":"15","author":"Segal","year":"2020","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/j.1600-065X.2006.00451.x","article-title":"Human natural killer cell development","volume":"214","author":"Freud","year":"2006","journal-title":"Immunol. Rev."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.celrep.2016.05.095","article-title":"NKp80 Defines a Critical Step during Human Natural Killer Cell Development","volume":"16","author":"Freud","year":"2016","journal-title":"Cell Rep."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/j.immuni.2017.10.008","article-title":"The Broad Spectrum of Human Natural Killer Cell Diversity","volume":"47","author":"Freud","year":"2017","journal-title":"Immunity"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1182\/blood-2007-09-077438","article-title":"Human natural killer cells","volume":"112","author":"Caligiuri","year":"2008","journal-title":"Blood"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"5166","DOI":"10.1073\/pnas.0800121105","article-title":"MiR-15a and miR-16-1 cluster functions in human leukemia","volume":"105","author":"Calin","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2806","DOI":"10.4049\/jimmunol.1500949","article-title":"MicroRNA-15\/16 Antagonizes Myb To Control NK Cell Maturation","volume":"195","author":"Sullivan","year":"2015","journal-title":"J. Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1084\/jem.20111386","article-title":"miR-150 regulates the development of NK and iNKT cells","volume":"208","author":"Bezman","year":"2011","journal-title":"J. Exp. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"6168","DOI":"10.4049\/jimmunol.0803036","article-title":"Notch activation induces the generation of functional NK cells from human cord blood CD34-positive cells devoid of IL-15","volume":"182","author":"Haraguchi","year":"2009","journal-title":"J. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1002\/JLB.1RU0518-197RR","article-title":"Noncoding RNA in NK cells","volume":"105","author":"Yang","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1182\/blood-2010-03-277012","article-title":"Genome-wide identification of human microRNAs located in leukemia-associated genomic alterations","volume":"117","author":"Starczynowski","year":"2011","journal-title":"Blood"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.exphem.2004.11.006","article-title":"Mechanisms of resistance to natural killer cell-mediated cytotoxicity in acute lymphoblastic leukemia","volume":"33","author":"Romanski","year":"2005","journal-title":"Exp. Hematol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2862","DOI":"10.1002\/eji.201444798","article-title":"microRNA management of NK-cell developmental and functional programs","volume":"44","author":"Leong","year":"2014","journal-title":"Eur. J. Immunol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"5331","DOI":"10.1182\/blood-2009-03-211938","article-title":"MicroRNA 29b functions in acute myeloid leukemia","volume":"114","author":"Garzon","year":"2009","journal-title":"Blood"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/1756-9966-30-110","article-title":"miR-15a and miR-16-1 inhibit the proliferation of leukemic cells by down-regulating WT1 protein level","volume":"30","author":"Gao","year":"2011","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1038\/leu.2015.327","article-title":"The TGF-beta\/SMAD pathway is an important mechanism for NK cell immune evasion in childhood B-acute lymphoblastic leukemia","volume":"30","author":"Rouce","year":"2016","journal-title":"Leukemia"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1111\/imr.13029","article-title":"Cell-intrinsic and -extrinsic roles of miRNAs in regulating T cell immunity","volume":"304","author":"Cho","year":"2021","journal-title":"Immunol. Rev."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"8461","DOI":"10.1002\/jcp.29689","article-title":"microRNAs involved in T-cell development, selection, activation, and hemostasis","volume":"235","author":"Tapeh","year":"2020","journal-title":"J. Cell Physiol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1159\/000496093","article-title":"Functional Role of MicroRNAs in Thymocyte Development","volume":"178","author":"Hu","year":"2019","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"7080","DOI":"10.1073\/pnas.0702409104","article-title":"MiR-150, a microRNA expressed in mature B and T cells, blocks early B cell development when expressed prematurely","volume":"104","author":"Zhou","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"6285","DOI":"10.1038\/s41388-018-0401-2","article-title":"Intrathymic Notch3 and CXCR4 combinatorial interplay facilitates T-cell leukemia propagation","volume":"37","author":"Ferrandino","year":"2018","journal-title":"Oncogene"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"100726","DOI":"10.1016\/j.currproblcancer.2021.100726","article-title":"Exosomal microRNA panels as biomarkers for hematological malignancies","volume":"45","author":"Moloudizargari","year":"2021","journal-title":"Curr. Probl. Cancer"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1084\/jem.20122516","article-title":"The TAL1 complex targets the FBXW7 tumor suppressor by activating miR-223 in human T cell acute lymphoblastic leukemia","volume":"210","author":"Mansour","year":"2013","journal-title":"J. Exp. Med."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Fragoso, R., Mao, T., Wang, S., Schaffert, S., Gong, X., Yue, S., Luong, R., Min, H., Yashiro-Ohtani, Y., and Davis, M. (2012). Modulating the strength and threshold of NOTCH oncogenic signals by mir-181a-1\/b-1. PLoS Genet., 8.","DOI":"10.1371\/journal.pgen.1002855"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.blre.2018.04.003","article-title":"T-cell acute lymphoblastic leukemia from miRNA perspective: Basic concepts, experimental approaches, and potential biomarkers","volume":"32","author":"Drobna","year":"2018","journal-title":"Blood Rev."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1038\/sj.leu.2402834","article-title":"TET1, a member of a novel protein family, is fused to MLL in acute myeloid leukemia containing the t(10;11)(q22;q23)","volume":"17","author":"Lorsbach","year":"2003","journal-title":"Leukemia"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Gebarowska, K., Mroczek, A., Kowalczyk, J.R., and Lejman, M. (2021). MicroRNA as a Prognostic and Diagnostic Marker in T-Cell Acute Lymphoblastic Leukemia. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22105317"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"64","DOI":"10.3389\/fmed.2015.00064","article-title":"Insights into Regulation of the miR-17-92 Cluster of miRNAs in Cancer","volume":"2","author":"Fuziwara","year":"2015","journal-title":"Front. Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1002\/kjm2.12352","article-title":"The depletion of Circ-PRKDC enhances autophagy and apoptosis in T-cell acute lymphoblastic leukemia via microRNA-653-5p\/Reelin mediation of the PI3K\/AKT\/mTOR signaling pathway","volume":"37","author":"Ling","year":"2021","journal-title":"Kaohsiung J. Med. Sci."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"8268","DOI":"10.18632\/oncotarget.6987","article-title":"MicroRNAs regulate TAL1 expression in T-cell acute lymphoblastic leukemia","volume":"7","author":"Correia","year":"2016","journal-title":"Oncotarget"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1126\/science.1079490","article-title":"Control of regulatory T cell development by the transcription factor Foxp3","volume":"299","author":"Hori","year":"2003","journal-title":"Science"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1084\/jem.20061692","article-title":"A role for Dicer in immune regulation","volume":"203","author":"Cobb","year":"2006","journal-title":"J. Exp. Med."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Haas, J.D., Nistala, K., Petermann, F., Saran, N., Chennupati, V., Schmitz, S., Korn, T., Wedderburn, L.R., Forster, R., and Krueger, A. (2011). Expression of miRNAs miR-133b and miR-206 in the Il17a\/f locus is co-regulated with IL-17 production in alphabeta and gammadelta T cells. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020171"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1189\/jlb.1VMR1216-505R","article-title":"The mazy case of Notch and immunoregulatory cells","volume":"102","author":"Grazioli","year":"2017","journal-title":"J. Leukoc. Biol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1186\/s13045-019-0797-3","article-title":"Myeloid-derived suppressor cells in hematological malignancies: Friends or foes","volume":"12","author":"Lv","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.humimm.2021.04.009","article-title":"The impact of microRNAs on myeloid-derived suppressor cells in cancer","volume":"82","author":"Baghbani","year":"2021","journal-title":"Hum. Immunol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1080\/16078454.2020.1843753","article-title":"Diagnostic, prognostic and predictive values of miR-100 and miR-210 in pediatric acute lymphoblastic Leukemia","volume":"25","author":"Hassan","year":"2020","journal-title":"Hematology"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"100800","DOI":"10.1016\/j.tranon.2020.100800","article-title":"MicroRNA Signatures in Blood or Bone Marrow Distinguish Subtypes of Pediatric Acute Lymphoblastic Leukemia","volume":"13","author":"Nair","year":"2020","journal-title":"Transl. Oncol."},{"key":"ref_128","first-page":"1104","article-title":"B-cell acute lymphoblastic leukemia-related microRNAs: Uncovering their diverse and special roles","volume":"11","author":"Lv","year":"2021","journal-title":"Am. J. Cancer Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/2\/829\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:27:32Z","timestamp":1760362052000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/2\/829"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,13]]},"references-count":128,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["ijms23020829"],"URL":"https:\/\/doi.org\/10.3390\/ijms23020829","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,13]]}}}