{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T15:51:07Z","timestamp":1779205867208,"version":"3.51.4"},"reference-count":139,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T00:00:00Z","timestamp":1639958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Histone methylation tightly regulates chromatin accessibility, transcription, proliferation, and cell differentiation, and its perturbation contributes to oncogenic reprogramming of cells. In particular, many myeloid malignancies show evidence of epigenetic dysregulation. Jumonji C (JmjC) domain-containing proteins comprise a large and diverse group of histone demethylases (KDMs), which remove methyl groups from lysines in histone tails and other proteins. Cumulating evidence suggests an emerging role for these demethylases in myeloid malignancies, rendering them attractive targets for drug interventions. In this review, we summarize the known functions of Jumonji C (JmjC) domain-containing proteins in myeloid malignancies. We highlight challenges in understanding the context-dependent mechanisms of these proteins and explore potential future pharmacological targeting.<\/jats:p>","DOI":"10.3390\/biom11121911","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T08:43:32Z","timestamp":1639989812000},"page":"1911","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The Cross Marks the Spot: The Emerging Role of JmjC Domain-Containing Proteins in Myeloid Malignancies"],"prefix":"10.3390","volume":"11","author":[{"given":"Hans Felix","family":"Staehle","sequence":"first","affiliation":[{"name":"Division of Molecular Hematology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, 79098 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heike Luise","family":"Pahl","sequence":"additional","affiliation":[{"name":"Division of Molecular Hematology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, 79098 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1977-153X","authenticated-orcid":false,"given":"Jonas Samuel","family":"Jutzi","sequence":"additional","affiliation":[{"name":"Division of Molecular Hematology, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, 79098 Freiburg, Germany"},{"name":"Division of Hematology, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston 02115, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/nrg1945","article-title":"JmjC-domain-containing proteins and histone demethylation","volume":"7","author":"Klose","year":"2006","journal-title":"Nat. Rev. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13045-019-0811-9","article-title":"LSD1\/KDM1A inhibitors in clinical trials: Advances and prospects","volume":"12","author":"Fang","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1038\/nrm3327","article-title":"Molecular mechanisms and potential functions of histone demethylases","volume":"13","author":"Kooistra","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1146\/annurev.biochem.78.070907.103946","article-title":"Reversal of Histone Methylation: Biochemical and Molecular Mechanisms of Histone Demethylases","volume":"79","author":"Mosammaparast","year":"2010","journal-title":"Annu. Rev. Biochem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1158\/0008-5472.CAN-08-1735","article-title":"Lysine-Specific Demethylase 1 Is Strongly Expressed in Poorly Differentiated Neuroblastoma: Implications for Therapy","volume":"69","author":"Schulte","year":"2009","journal-title":"Cancer Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.cell.2006.04.024","article-title":"Structural Insights into Histone Demethylation by JMJD2 Family Members","volume":"125","author":"Chen","year":"2006","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1515\/bmc-2014-0010","article-title":"The Jumonji family: Past, present and future of histone demethylases in cancer","volume":"5","author":"Franci","year":"2014","journal-title":"Biomol. Concepts"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.sbi.2016.05.013","article-title":"Structure\u2013function relationships of human JmjC oxygenases\u2014demethylases versus hydroxylases","volume":"41","author":"Markolovic","year":"2016","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_9","first-page":"1","article-title":"The cancer driver genes IDH1\/2, JARID1C\/ KDM5C, and UTX\/ KDM6A: Crosstalk between histone demethylation and hypoxic reprogramming in cancer metabolism","volume":"51","author":"Chang","year":"2019","journal-title":"Exp. Mol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1158\/2159-8290.CD-16-0058","article-title":"ASH1L Links Histone H3 Lysine 36 Dimethylation to MLL Leukemia","volume":"6","author":"Zhu","year":"2016","journal-title":"Cancer Discov."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1002\/mc.20878","article-title":"JmjC-domain containing histone demethylase 1B-mediated p15 Ink4b suppression promotes the proliferation of leukemic progenitor cells through modulation of cell cycle progression in acute myeloid leukemia","volume":"52","author":"Nakamura","year":"2011","journal-title":"Mol. Carcinog."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3869","DOI":"10.1182\/blood-2010-10-312736","article-title":"KDM2b\/JHDM1b, an H3K36me2-specific demethylase, is required for initiation and maintenance of acute myeloid leukemia","volume":"117","author":"He","year":"2011","journal-title":"Blood"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.cbi.2009.12.005","article-title":"Hematopoietic neoplastic diseases develop in C3H\/He and C57BL\/6 mice after benzene exposure: Strain differences in bone marrow tissue responses observed using microarrays","volume":"184","author":"Inoue","year":"2010","journal-title":"Chem. Interact."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3539","DOI":"10.4161\/cc.7.22.7062","article-title":"KDM2A represses transcription of centromeric satellite repeats and maintains the heterochromatic state","volume":"7","author":"Frescas","year":"2008","journal-title":"Cell Cycle"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"10024","DOI":"10.1158\/0008-5472.CAN-08-2208","article-title":"Chromosomal Rearrangements Leading to MLL Gene Fusions: Clinical and Biological Aspects","volume":"68","author":"Harper","year":"2008","journal-title":"Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.celrep.2015.12.034","article-title":"Non-canonical PRC1.1 Targets Active Genes Independent of H3K27me3 and Is Essential for Leukemogenesis","volume":"14","author":"Boom","year":"2016","journal-title":"Cell Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3437","DOI":"10.1182\/blood-2014-03-562694","article-title":"Fbxl10 overexpression in murine hematopoietic stem cells induces leukemia involving metabolic activation and upregulation of Nsg2","volume":"125","author":"Ueda","year":"2015","journal-title":"Blood"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Karoopongse, E., Yeung, C., Byon, J., Ramakrishnan, A., Holman, Z.J., Jiang, P.Y.Z., Yu, Q., Deeg, H.J., and Marcondes, A.M. (2014). The KDM2B- Let-7b -EZH2 Axis in Myelodysplastic Syndromes as a Target for Combined Epigenetic Therapy. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0107817"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1172\/JCI84014","article-title":"Histone demethylase KDM2B regulates lineage commitment in normal and malignant hematopoiesis","volume":"126","author":"Andricovich","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.exphem.2019.07.002","article-title":"Transcription factor Oct1 protects against hematopoietic stress and promotes acute myeloid leukemia","volume":"76","author":"Jafek","year":"2019","journal-title":"Exp. Hematol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12935-019-0979-7","article-title":"KDM3B suppresses APL progression by restricting chromatin accessibility and facilitating the ATRA-mediated degradation of PML\/RAR\u03b1","volume":"19","author":"Wang","year":"2019","journal-title":"Cancer Cell Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1080\/10428194.2017.1324156","article-title":"KDM3B shows tumor-suppressive activity and transcriptionally regulates HOXA1 through retinoic acid response elements in acute myeloid leukemia","volume":"59","author":"Xu","year":"2018","journal-title":"Leuk. Lymphoma"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6946","DOI":"10.1038\/sj.onc.1204850","article-title":"A novel nuclear protein, 5qNCA (LOC51780) is a candidate for the myeloid leukemia tumor suppressor gene on chromosome 5 band q31","volume":"20","author":"Hu","year":"2001","journal-title":"Oncogene"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1002\/2211-5463.13054","article-title":"Modulators of histone demethylase JMJD1C selectively target leukemic stem cells","volume":"11","author":"Yang","year":"2021","journal-title":"FEBS Open Bio"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1097\/FPC.0000000000000422","article-title":"JMJD1C knockdown affects myeloid cell lines proliferation, viability, and gemcitabine\/carboplatin-sensitivity","volume":"31","author":"Schimek","year":"2021","journal-title":"Pharmacogenet. Genom."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Staehle, H.F., Heinemann, J., Gruender, A., Omlor, A.M., Pahl, H.L., and Jutzi, J.S. (2020). Jmjd1c is dispensable for healthy adult hematopoiesis and Jak2V617F-driven myeloproliferative disease initiation in mice. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0228362"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1002\/ijc.32552","article-title":"Small molecular modulators of JMJD1C preferentially inhibit growth of leukemia cells","volume":"146","author":"Xu","year":"2020","journal-title":"Int. J. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1182\/bloodadvances.2018026054","article-title":"Critical role of Jumonji domain of JMJD1C in MLL-rearranged leukemia","volume":"3","author":"Christiansen","year":"2019","journal-title":"Blood Adv."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1038\/s41375-018-0354-z","article-title":"JMJD1C-mediated metabolic dysregulation contributes to HOXA9-dependent leukemogenesis","volume":"33","author":"Lynch","year":"2019","journal-title":"Leukemia"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1182\/blood-2017-10-810622","article-title":"Epigenetic regulation of NFE2 overexpression in myeloproliferative neoplasms","volume":"131","author":"Peeken","year":"2018","journal-title":"Blood"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1172\/JCI82978","article-title":"MLL-AF9\u2013 and HOXA9-mediated acute myeloid leukemia stem cell self-renewal requires JMJD1C","volume":"126","author":"Zhu","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1101\/gad.267278.115","article-title":"JMJD1C is required for the survival of acute myeloid leukemia by functioning as a coactivator for key transcription factors","volume":"29","author":"Chen","year":"2015","journal-title":"Genes Dev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1182\/blood-2013-08-522094","article-title":"shRNA screening identifies JMJD1C as being required for leukemia maintenance","volume":"123","author":"Sroczynska","year":"2014","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1101\/gad.280495.116","article-title":"Jmjd2\/Kdm4 demethylases are required for expression of Il3ra and survival of acute myeloid leukemia cells","volume":"30","author":"Agger","year":"2016","journal-title":"Genes Dev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41419-021-03738-0","article-title":"A KDM4A-PAF1-mediated epigenomic network is essential for acute myeloid leukemia cell self-renewal and survival","volume":"12","author":"Massett","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7499","DOI":"10.1038\/sj.onc.1210582","article-title":"Human RNA polymerase II-associated factor complex: Dysregulation in cancer","volume":"26","author":"Chaudhary","year":"2007","journal-title":"Oncogene"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Milan, T., Celton, M., Lagac\u00e9, K., Roques, \u00c9., Safa-Tahar-Henni, S., Bresson, E., Bergeron, A., Hebert, J., Meshinchi, S., and Cellot, S. (2020). Epigenetic changes in human model KMT2A leukemias highlight early events during leukemogenesis. Haematologica.","DOI":"10.3324\/haematol.2020.271619"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2040622321997259","DOI":"10.1177\/2040622321997259","article-title":"KDM4C contributes to cytarabine resistance in acute myeloid leukemia via regulating the miR-328-3p\/CCND2 axis through MALAT1","volume":"12","author":"Xue","year":"2021","journal-title":"Ther. Adv. Chronic Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.stem.2020.04.001","article-title":"Leukemogenic Chromatin Alterations Promote AML Leukemia Stem Cells via a KDM4C-ALKBH5-AXL Signaling Axis","volume":"27","author":"Wang","year":"2020","journal-title":"Cell Stem Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.ccell.2015.12.007","article-title":"Targeting Aberrant Epigenetic Networks Mediated by PRMT1 and KDM4C in Acute Myeloid Leukemia","volume":"29","author":"Cheung","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3043","DOI":"10.1158\/0008-5472.CAN-13-2321","article-title":"LEO1 Is Regulated by PRL-3 and Mediates Its Oncogenic Properties in Acute Myelogenous Leukemia","volume":"74","author":"Chong","year":"2014","journal-title":"Cancer Res."},{"key":"ref_42","first-page":"2308","article-title":"Overexpression of KDM4D promotes acute myeloid leukemia cell development by activating MCL-1","volume":"13","author":"Wu","year":"2021","journal-title":"Am. J. Transl. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2280","DOI":"10.1038\/leu.2013.87","article-title":"NUP98\/JARID1A is a novel recurrent abnormality in pediatric acute megakaryoblastic leukemia with a distinct HOX gene expression pattern","volume":"27","author":"Hollink","year":"2013","journal-title":"Leukemia"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.18632\/oncotarget.2859","article-title":"Histone demethylase RBP2 decreases miR-21 in blast crisis of chronic myeloid leukemia","volume":"6","author":"Zhou","year":"2014","journal-title":"Oncotarget"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"654411","DOI":"10.3389\/fonc.2021.654411","article-title":"miR-181d\/RBP2\/NF-\u03baB p65 Feedback Regulation Promotes Chronic Myeloid Leukemia Blast Crisis","volume":"11","author":"Zhou","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.exphem.2020.01.006","article-title":"Histone lysine demethylase KDM5B maintains chronic myeloid leukemia via multiple epigenetic actions","volume":"82","author":"Xue","year":"2020","journal-title":"Exp. Hematol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.ccell.2015.06.003","article-title":"The H3K4-Methyl Epigenome Regulates Leukemia Stem Cell Oncogenic Potential","volume":"28","author":"Wong","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"657191","DOI":"10.3389\/fonc.2021.657191","article-title":"Personalized Survival Prediction of Patients With Acute Myeloblastic Leukemia Using Gene Expression Profiling","volume":"11","author":"Orgueira","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1182\/blood-2014-08-596734","article-title":"The histone demethylase Jarid1b is required for hematopoietic stem cell self-renewal in mice","volume":"125","author":"Stewart","year":"2015","journal-title":"Blood"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1182\/blood-2013-04-496281","article-title":"RNAi screen identifies Jarid1b as a major regulator of mouse HSC activity","volume":"122","author":"Cellot","year":"2013","journal-title":"Blood"},{"key":"ref_51","first-page":"177","article-title":"mRNA expression profiling of histone modifying enzymes in pediatric acute monoblastic leukemia","volume":"72","author":"Xiao","year":"2017","journal-title":"Die Pharm. Int. J. Pharm. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.leukres.2017.12.001","article-title":"Whole exome sequencing identifies novel mutations of epigenetic regulators in chemorefractory pediatric acute myeloid leukemia","volume":"65","author":"Zhan","year":"2018","journal-title":"Leuk. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1038\/s41375-018-0011-6","article-title":"Utx loss causes myeloid transformation","volume":"32","author":"Zheng","year":"2018","journal-title":"Leukemia"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.1182\/blood-2012-08-452003","article-title":"The histone demethylase UTX regulates stem cell migration and hematopoiesis","volume":"121","author":"Thieme","year":"2013","journal-title":"Blood"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1038\/s41588-018-0114-z","article-title":"UTX-mediated enhancer and chromatin remodeling suppresses myeloid leukemogenesis through noncatalytic inverse regulation of ETS and GATA programs","volume":"50","author":"Gozdecka","year":"2018","journal-title":"Nat. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/s41375-019-0497-6","article-title":"Loss of KDM6A confers drug resistance in acute myeloid leukemia","volume":"34","author":"Stief","year":"2020","journal-title":"Leukemia"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2691","DOI":"10.7150\/thno.50571","article-title":"KDM6A promotes imatinib resistance through YY1-mediated transcriptional upregulation of TRKA independently of its demethylase activity in chronic myelogenous leukemia","volume":"11","author":"Zhang","year":"2021","journal-title":"Theranostics"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.exphem.2012.01.017","article-title":"A functional role for the histone demethylase UTX in normal and malignant hematopoietic cells","volume":"40","author":"Liu","year":"2012","journal-title":"Exp. Hematol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5268","DOI":"10.1096\/fj.201801035R","article-title":"MBD3\/NuRD loss participates with KDM6A program to promoteDOCK5\/8expression and Rac GTPase activation in human acute myeloid leukemia","volume":"33","author":"Biswas","year":"2019","journal-title":"FASEB J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1038\/leu.2013.91","article-title":"Global H3K4me3 genome mapping reveals alterations of innate immunity signaling and overexpression of JMJD3 in human myelodysplastic syndrome CD34+ cells","volume":"27","author":"Wei","year":"2013","journal-title":"Leukemia"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1007\/s00432-018-2631-7","article-title":"Therapeutic potential of GSK-J4, a histone demethylase KDM6B\/JMJD3 inhibitor, for acute myeloid leukemia","volume":"144","author":"Li","year":"2018","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2491","DOI":"10.1182\/bloodadvances.2018024166","article-title":"KDM6B overexpression activates innate immune signaling and impairs hematopoiesis in mice","volume":"2","author":"Wei","year":"2018","journal-title":"Blood Adv."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2506","DOI":"10.1038\/s41375-019-0462-4","article-title":"Kdm6b regulates context-dependent hematopoietic stem cell self-renewal and leukemogenesis","volume":"33","author":"Mallaney","year":"2019","journal-title":"Leukemia"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1515\/hsz-2020-0345","article-title":"JMJD3-regulated expression of IL-6 is involved in the proliferation and chemosensitivity of acute myeloid leukemia cells","volume":"402","author":"Xu","year":"2019","journal-title":"Biol. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-018-05548-z","article-title":"JMJD3 facilitates C\/EBP\u03b2-centered transcriptional program to exert oncorepressor activity in AML","volume":"9","author":"Yu","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4177","DOI":"10.1038\/ncomms5177","article-title":"Ezh2 loss promotes development of myelodysplastic syndrome but attenuates its predisposition to leukaemic transformation","volume":"5","author":"Sashida","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2779","DOI":"10.1038\/s41375-019-0617-3","article-title":"The functional mechanisms of mutations in myelodysplastic syndrome","volume":"33","author":"Nagata","year":"2019","journal-title":"Leukemia"},{"key":"ref_68","first-page":"1","article-title":"Integrative study of EZH2 mutational status, copy number, protein expression and H3K27 trimethylation in AML\/MDS patients","volume":"13","author":"Stomper","year":"2021","journal-title":"Clin. Epigenet."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2496","DOI":"10.1056\/NEJMoa1013343","article-title":"Clinical Effect of Point Mutations in Myelodysplastic Syndromes","volume":"364","author":"Bejar","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"The Cancer Genome Atlas Research Network (2013). Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N. Engl. J. Med., 368, 2059\u20132074.","DOI":"10.1056\/NEJMoa1301689"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1038\/nm.3909","article-title":"The prognostic landscape of genes and infiltrating immune cells across human cancers","volume":"21","author":"Gentles","year":"2015","journal-title":"Nat. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1101\/gad.191163.112","article-title":"A complex Polycomb issue: The two faces of EZH2 in cancer","volume":"26","author":"Hock","year":"2012","journal-title":"Genes Dev."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1038\/ng.3420","article-title":"Juvenile myelomonocytic leukemia displays mutations in components of the RAS pathway and the PRC2 network","volume":"47","author":"Caye","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1172\/JCI30182","article-title":"The homeobox gene CDX2 is aberrantly expressed in most cases of acute myeloid leukemia and promotes leukemogenesis","volume":"117","author":"Scholl","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1073\/pnas.0305555101","article-title":"Ectopic expression of the homeobox gene Cdx2 is the transforming event in a mouse model of t(12;13)(p13;q12) acute myeloid leukemia","volume":"101","author":"Rawat","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.cancergen.2011.02.001","article-title":"A cryptic deletion in 5q31.2 provides further evidence for a minimally deleted region in myelodysplastic syndromes","volume":"204","author":"MacKinnon","year":"2011","journal-title":"Cancer Genet."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.ccr.2009.12.045","article-title":"PML\/RAR\u03b1 Targets Promoter Regions Containing PU.1 Consensus and RARE Half Sites in Acute Promyelocytic Leukemia","volume":"17","author":"Wang","year":"2010","journal-title":"Cancer Cell"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/1756-8722-6-25","article-title":"Structurally differentiated cis-elements that interact with PU.1 are functionally distinguishable in acute promyelocytic leukemia","volume":"6","author":"Qian","year":"2013","journal-title":"J. Hematol. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1182\/blood-2009-11-254664","article-title":"AML1 is overexpressed in patients with myeloproliferative neoplasms and mediates JAK2V617F-independent overexpression of NF-E2","volume":"116","author":"Wang","year":"2010","journal-title":"Blood"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1111\/j.1365-2141.2005.05416.x","article-title":"Gene expression profiling in polycythaemia vera: Overexpression of transcription factor NF-E2","volume":"129","author":"Goerttler","year":"2005","journal-title":"Br. J. Haematol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1084\/jem.20110540","article-title":"A novel murine model of myeloproliferative disorders generated by overexpression of the transcription factor NF-E2","volume":"209","author":"Kaufmann","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1084\/jem.20120521","article-title":"MPN patients harbor recurrent truncating mutations in transcription factor NF-E2","volume":"210","author":"Jutzi","year":"2013","journal-title":"J. Exp. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1182\/blood-2018-09-875047","article-title":"Altered NFE2 activity predisposes to leukemic transformation and myelosarcoma with AML-specific aberrations","volume":"133","author":"Jutzi","year":"2019","journal-title":"Blood"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.15252\/embj.201593317","article-title":"Continual removal of H3K9 promoter methylation by Jmjd2 demethylases is vital for ESC self-renewal and early development","volume":"35","author":"Pedersen","year":"2016","journal-title":"EMBO J."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1128\/MCB.00864-13","article-title":"The Demethylase JMJD2C Localizes to H3K4me3-Positive Transcription Start Sites and Is Dispensable for Embryonic Development","volume":"34","author":"Pedersen","year":"2014","journal-title":"Mol. Cell. Biol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1182\/blood.2019000855","article-title":"The KDM4\/JMJD2 histone demethylases are required for hematopoietic stem cell maintenance","volume":"134","author":"Agger","year":"2019","journal-title":"Blood"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"D881","DOI":"10.1093\/nar\/gky1076","article-title":"BloodSpot: A database of healthy and malignant haematopoiesis updated with purified and single cell mRNA sequencing profiles","volume":"47","author":"Bagger","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1111\/j.1600-065X.2012.01164.x","article-title":"The GM-CSF\/IL-3\/IL-5 cytokine receptor family: From ligand recognition to initiation of signaling","volume":"250","author":"Broughton","year":"2012","journal-title":"Immunol. Rev."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/2050-7771-2-4","article-title":"CD 123 is a membrane biomarker and a therapeutic target in hematologic malignancies","volume":"2","author":"Testa","year":"2014","journal-title":"Biomark. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/onc.2017.337","article-title":"The PAF complex regulation of Prmt5 facilitates the progression and maintenance of MLL fusion leukemia","volume":"37","author":"Serio","year":"2018","journal-title":"Oncogene"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.ccr.2010.04.012","article-title":"The PAF Complex Synergizes with MLL Fusion Proteins at HOX Loci to Promote Leukemogenesis","volume":"17","author":"Muntean","year":"2010","journal-title":"Cancer Cell"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"312","DOI":"10.3389\/fchem.2020.00312","article-title":"A New Family of Jumonji C Domain-Containing KDM Inhibitors Inspired by Natural Product Purpurogallin","volume":"8","author":"Souto","year":"2020","journal-title":"Front. Chem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1182\/blood-2016-09-738005","article-title":"S100A9 induces differentiation of acute myeloid leukemia cells through TLR4","volume":"129","author":"Laouedj","year":"2017","journal-title":"Blood"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbrc.2018.09.034","article-title":"LncRNA MALAT1 promotes cell proliferation and imatinib resistance by sponging miR-328 in chronic myelogenous leukemia","volume":"507","author":"Wen","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.omtn.2019.02.017","article-title":"lncRNA TUG1 Promotes Cisplatin Resistance by Regulating CCND2 via Epigenetically Silencing miR-194-5p in Bladder Cancer","volume":"16","author":"Yu","year":"2019","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Zhou, J., Bi, C., Chng, W.-J., Cheong, L.-L., Liu, S.-C., Mahara, S., Tay, K.-G., Zeng, Q., Li, J., and Guo, K. (2011). PRL-3, a Metastasis Associated Tyrosine Phosphatase, Is Involved in FLT3-ITD Signaling and Implicated in Anti-AML Therapy. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0019798"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"9235","DOI":"10.1073\/pnas.1404303111","article-title":"Chem-seq permits identification of genomic targets of drugs against androgen receptor regulation selected by functional phenotypic screens","volume":"111","author":"Jin","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/j.ccell.2018.10.014","article-title":"KDM5 Histone Demethylase Activity Links Cellular Transcriptomic Heterogeneity to Therapeutic Resistance","volume":"34","author":"Hinohara","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"112314","DOI":"10.1016\/j.yexcr.2020.112314","article-title":"Molecular mechanisms of KDM5A in cellular functions: Facets during development and disease","volume":"396","author":"Kirtana","year":"2020","journal-title":"Exp. Cell Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1002\/gcc.20308","article-title":"Identification ofNUP98 abnormalities in acute leukemia:JARID1A (12p13) as a new partner gene","volume":"45","author":"Velthuizen","year":"2006","journal-title":"Genes Chromosom. Cancer"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1093\/jnci\/djx207","article-title":"Role of RBP2-Induced ER and IGF1R-ErbB Signaling in Tamoxifen Resistance in Breast Cancer","volume":"110","author":"Choi","year":"2017","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"3307","DOI":"10.1182\/bloodadvances.2019030981","article-title":"Human models of NUP98-KDM5A megakaryocytic leukemia in mice contribute to uncovering new biomarkers and therapeutic vulnerabilities","volume":"3","author":"Cardin","year":"2019","journal-title":"Blood Adv."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1111\/bjh.16203","article-title":"Patients aged less than 3 years with acute myeloid leukaemia characterize a molecularly and clinically distinct subgroup","volume":"188","author":"Hara","year":"2020","journal-title":"Br. J. Haematol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1002\/gcc.22444","article-title":"Prognostic impact of specific molecular profiles in pediatric acute megakaryoblastic leukemia in non-Down syndrome","volume":"56","author":"Hara","year":"2017","journal-title":"Genes Chromosom. Cancer"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/ng.3772","article-title":"Pediatric non\u2013Down syndrome acute megakaryoblastic leukemia is characterized by distinct genomic subsets with varying outcomes","volume":"49","author":"Branstetter","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_106","first-page":"364","article-title":"The PHD finger: A versatile epigenome reader","volume":"36","author":"Sanchez","year":"2011","journal-title":"Trends Biochem. Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1158\/2159-8290.CD-13-0419","article-title":"NUP98\u2013PHF23 Is a Chromatin-Modifying Oncoprotein That Causes a Wide Array of Leukemias Sensitive to Inhibition of PHD Histone Reader Function","volume":"4","author":"Gough","year":"2014","journal-title":"Cancer Discov."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"296","DOI":"10.3389\/fonc.2020.00296","article-title":"Increased HDAC Activity and c-MYC Expression Mediate Acquired Resistance to WEE1 Inhibition in Acute Leukemia","volume":"10","author":"Garcia","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.3892\/mmr.2017.6960","article-title":"KDM5A promotes proliferation and EMT in ovarian cancer and closely correlates with PTX resistance","volume":"16","author":"Feng","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1053\/j.gastro.2009.10.004","article-title":"The Histone Demethylase RBP2 Is Overexpressed in Gastric Cancer and Its Inhibition Triggers Senescence of Cancer Cells","volume":"138","author":"Zeng","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_111","first-page":"247","article-title":"Genomic amplification and a role in drug-resistance for the KDM5A histone demethylase in breast cancer","volume":"4","author":"Hou","year":"2012","journal-title":"Am. J. Transl. Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"4711","DOI":"10.1158\/0008-5472.CAN-12-3165","article-title":"Histone Demethylase RBP2 Promotes Lung Tumorigenesis and Cancer Metastasis","volume":"73","author":"Teng","year":"2013","journal-title":"Cancer Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/nchembio.2085","article-title":"An inhibitor of KDM5 demethylases reduces survival of drug-tolerant cancer cells","volume":"12","author":"Vinogradova","year":"2016","journal-title":"Nat. Chem. Biol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.cell.2010.02.027","article-title":"A Chromatin-Mediated Reversible Drug-Tolerant State in Cancer Cell Subpopulations","volume":"141","author":"Sharma","year":"2010","journal-title":"Cell"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"3418","DOI":"10.1080\/15384101.2015.1090063","article-title":"The histone demethylase KDM5A is a key factor for the resistance to temozolomide in glioblastoma","volume":"14","author":"Banelli","year":"2015","journal-title":"Cell Cycle"},{"key":"ref_116","first-page":"1071","article-title":"Expression Levels of JARID1B, Hes1 and MMP-9 Genes in CML Patients Treated with Imatinib Mesylate","volume":"7","author":"He","year":"2019","journal-title":"Europe"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.semcancer.2018.11.001","article-title":"KDM5B is a master regulator of the H3K4-methylome in stem cells, development and cancer","volume":"57","author":"Xhabija","year":"2019","journal-title":"Semin. Cancer Biol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13058-019-1228-7","article-title":"Inhibition of the histone demethylase, KDM5B, directly induces re-expression of tumor suppressor protein HEXIM1 in cancer cells","volume":"21","author":"Montano","year":"2019","journal-title":"Breast Cancer Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"4450","DOI":"10.1038\/emboj.2011.317","article-title":"Epigenetic silencing of the oncogenic miR-17-92 cluster during PU.1-directed macrophage differentiation","volume":"30","author":"Pospisil","year":"2011","journal-title":"EMBO J."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.celrep.2017.03.035","article-title":"Structure of Nascent Chromatin Is Essential for Hematopoietic Lineage Specification","volume":"19","author":"Petruk","year":"2017","journal-title":"Cell Rep."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-021-81890-5","article-title":"Clonal hematopoiesis in adult pure red cell aplasia","volume":"11","author":"Fujishima","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"102535","DOI":"10.1016\/j.bcmd.2021.102535","article-title":"Comparative Analysis of the Genetic Variants in Haematopoietic Stem\/Progenitor and Mesenchymal Stem Cell Compartments in de novo Myelodysplastic Syndromes","volume":"88","author":"Bandara","year":"2021","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1158\/1078-0432.CCR-17-2344","article-title":"Evolution of Cytogenetically Normal Acute Myeloid Leukemia During Therapy and Relapse: An Exome Sequencing Study of 50 Patients","volume":"24","author":"Greif","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"3932","DOI":"10.1182\/blood-2010-10-311019","article-title":"Mutational spectrum analysis of chronic myelomonocytic leukemia includes genes associated with epigenetic regulation: UTX, EZH2, and DNMT3A","volume":"118","author":"Jankowska","year":"2011","journal-title":"Blood"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1172\/JCI45284","article-title":"Sequencing a mouse acute promyelocytic leukemia genome reveals genetic events relevant for disease progression","volume":"121","author":"Wartman","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"10954","DOI":"10.1128\/MCB.24.24.10954-10964.2004","article-title":"Ras\/Mitogen-Activated Protein Kinase Signaling Activates Ets-1 and Ets-2 by CBP\/p300 Recruitment","volume":"24","author":"Foulds","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41392-019-0040-2","article-title":"Epigenetic drug library screening identified an LSD1 inhibitor to target UTX-deficient cells for differentiation therapy","volume":"4","author":"Wu","year":"2019","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.exphem.2017.10.002","article-title":"KDM6 and KDM4 histone lysine demethylases emerge as molecular therapeutic targets in human acute myeloid leukemia","volume":"58","author":"Boila","year":"2018","journal-title":"Exp. Hematol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/S0092-8674(00)81113-7","article-title":"Nerve Growth Factor Is an Autocrine Survival Factor for Memory B Lymphocytes","volume":"85","author":"Torcia","year":"1996","journal-title":"Cell"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/s41571-018-0113-0","article-title":"NTRK fusion-positive cancers and TRK inhibitor therapy","volume":"15","author":"Cocco","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.1038\/s41375-019-0576-8","article-title":"Revisiting NTRKs as an emerging oncogene in hematological malignancies","volume":"33","author":"Joshi","year":"2019","journal-title":"Leukemia"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1038\/bjc.2015.274","article-title":"Anti-apoptotic role and clinical relevance of neurotrophins in diffuse large B-cell lymphomas","volume":"113","author":"Dubanet","year":"2015","journal-title":"Br. J. Cancer"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.1182\/blood-2008-05-155200","article-title":"High-affinity neurotrophin receptors and ligands promote leukemogenesis","volume":"113","author":"Li","year":"2009","journal-title":"Blood"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1182\/blood-2009-10-247437","article-title":"Rac2 GTPase deficiency depletes BCR-ABL+ leukemic stem cells and progenitors in vivo","volume":"116","author":"Sengupta","year":"2010","journal-title":"Blood"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.celrep.2017.04.016","article-title":"Targeting Ras-Driven Cancer Cell Survival and Invasion through Selective Inhibition of DOCK1","volume":"19","author":"Tajiri","year":"2017","journal-title":"Cell Rep."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.ccr.2007.10.015","article-title":"Rac Guanosine Triphosphatases Represent Integrating Molecular Therapeutic Targets for BCR-ABL-Induced Myeloproliferative Disease","volume":"12","author":"Thomas","year":"2007","journal-title":"Cancer Cell"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-019-10652-9","article-title":"Targeting enhancer switching overcomes non-genetic drug resistance in acute myeloid leukaemia","volume":"10","author":"Bell","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1038\/nrc3599","article-title":"Cancer drug resistance: An evolving paradigm","volume":"13","author":"Holohan","year":"2013","journal-title":"Nat. Rev. Cancer"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/nature22993","article-title":"Tracing the origins of relapse in acute myeloid leukaemia to stem cells","volume":"547","author":"Shlush","year":"2017","journal-title":"Nature"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/12\/1911\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:49:56Z","timestamp":1760168996000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/12\/1911"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,20]]},"references-count":139,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["biom11121911"],"URL":"https:\/\/doi.org\/10.3390\/biom11121911","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,20]]}}}