{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T20:05:45Z","timestamp":1785355545596,"version":"3.55.0"},"reference-count":40,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,4]],"date-time":"2020-06-04T00:00:00Z","timestamp":1591228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Progetti di Ricerca Corrente"],"award-info":[{"award-number":["Progetti di Ricerca Corrente"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Leukocytes are major cellular components of the inflammatory and immune response systems. After their generation in the bone marrow from hematopoietic stem cells, they maturate as granulocytes (neutrophils, eosinophils, and basophils), monocytes, and lymphocytes. The abnormal accumulation and proliferation of immature blood cells (blasts) lead to severe and widespread diseases such as leukemia. We have recently shown that KCTD15, a member of the potassium channel tetramerization domain containing protein family (KCTD), is remarkably upregulated in leukemic B-cells. Here, we extend our investigation by monitoring the KCTD15 expression levels in circulating lymphocytes, monocytes, and granulocytes, as well as in leukemia cells. Significant differences in the expression level of KCTD15 were detected in normal lymphocytes, monocytes, and granulocytes. Interestingly, we also found overexpression of the protein following leukemic transformation in the case of myeloid cell lineage. Indeed, KCTD15 was found to be upregulated in K562 and NB4 cells, as well as in HL-60 cell lines. This in vitro finding was corroborated by the analysis of KCTD15 mRNA of acute myeloid leukemia (AML) patients reported in the Microarray Innovations in Leukemia (MILE) dataset. Collectively, the present data open interesting perspectives for understanding the maturation process of leukocytes and for the diagnosis\/therapy of acute leukemias.<\/jats:p>","DOI":"10.3390\/diagnostics10060371","type":"journal-article","created":{"date-parts":[[2020,6,5]],"date-time":"2020-06-05T03:32:21Z","timestamp":1591327941000},"page":"371","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["KCTD15 Protein Expression in Peripheral Blood and Acute Myeloid Leukemia"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1989-4740","authenticated-orcid":false,"given":"Giovanni","family":"Smaldone","sequence":"first","affiliation":[{"name":"IRCCS SDN, Napoli, Via E. Gianturco 113, 80143 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Coppola","sequence":"additional","affiliation":[{"name":"IRCCS SDN, Napoli, Via E. Gianturco 113, 80143 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7019-0581","authenticated-orcid":false,"given":"Mariarosaria","family":"Incoronato","sequence":"additional","affiliation":[{"name":"IRCCS SDN, Napoli, Via E. Gianturco 113, 80143 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanna","family":"Parasole","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology-Oncology, Santobono-Pausilipon Hospital, 80129 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mimmo","family":"Ripaldi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology-Oncology, Santobono-Pausilipon Hospital, 80129 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Vitagliano","sequence":"additional","affiliation":[{"name":"Institute of Biostructures and Bioimaging, C.N.R., 80134 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peppino","family":"Mirabelli","sequence":"additional","affiliation":[{"name":"IRCCS SDN, Napoli, Via E. Gianturco 113, 80143 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9734-7702","authenticated-orcid":false,"given":"Marco","family":"Salvatore","sequence":"additional","affiliation":[{"name":"IRCCS SDN, Napoli, Via E. Gianturco 113, 80143 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.jaci.2009.12.980","article-title":"Overview of the immune response","volume":"125","author":"Chaplin","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4273943","DOI":"10.1155\/2016\/4273943","article-title":"The Immune System in Cancer Pathogenesis: Potential Therapeutic Approaches","volume":"2016","author":"Pandya","year":"2016","journal-title":"J. Immunol. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1242\/dev.134866","article-title":"Human haematopoietic stem cell development: From the embryo to the dish","volume":"144","author":"Ivanovs","year":"2017","journal-title":"Development"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/978-3-030-24108-7_10","article-title":"Hematopoietic Stem Cell Heterogeneity","volume":"1169","author":"Jurecic","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1146\/annurev.iy.12.040194.000505","article-title":"CD45: An emerging role as a protein tyrosine phosphatase required for lymphocyte activation and development","volume":"12","author":"Trowbridge","year":"1994","journal-title":"Annu. Rev. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1093\/intimm\/8.11.1743","article-title":"CD45 up-regulation during lymphocyte maturation","volume":"8","author":"Kirberg","year":"1996","journal-title":"Int. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"217","DOI":"10.3109\/10428199609051610","article-title":"CD45 (leucocyte common antigen) expression in T and B lymphocyte subsets","volume":"20","author":"Poppema","year":"1996","journal-title":"Leuk. Lymphoma"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1002\/cyto.b.21530","article-title":"Monocytes and macrophages in flow cytometry","volume":"92","author":"Lambert","year":"2017","journal-title":"Cytom. B Clin. Cytom."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Marimuthu, R., Francis, H., Dervish, S., Li, S.C.H., Medbury, H., and Williams, H. (2018). Characterization of Human Monocyte Subsets by Whole Blood Flow Cytometry Analysis. J. Vis. Exp.","DOI":"10.3791\/57941"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1182\/blood-2016-03-643544","article-title":"The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia","volume":"127","author":"Arber","year":"2016","journal-title":"Blood"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1053\/j.seminhematol.2018.08.002","article-title":"The 2016 WHO classification of acute myeloid leukemia: What the practicing clinician needs to know","volume":"56","author":"Arber","year":"2019","journal-title":"Semin. Hematol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1002\/bies.201300002","article-title":"Protein partners of KCTD proteins provide insights about their functional roles in cell differentiation and vertebrate development","volume":"35","author":"Skoblov","year":"2013","journal-title":"Bioessays"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1111\/cns.13156","article-title":"KCTD: A new gene family involved in neurodevelopmental and neuropsychiatric disorders","volume":"25","author":"Teng","year":"2019","journal-title":"CNS Neurosci. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"20108","DOI":"10.1038\/s41598-019-56701-7","article-title":"KCTD15 is overexpressed in human childhood B-cell acute lymphoid leukemia","volume":"9","author":"Smaldone","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_15","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_16","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/sj.leu.2404412","article-title":"Flow cytometry analysis of acute promyelocytic leukemia: The power of \u2018surface hematology\u2019","volume":"21","author":"Mirabelli","year":"2007","journal-title":"Leukemia"},{"key":"ref_17","first-page":"14","article-title":"Polychromatic flow cytometry analysis of CD34+ hematopoietic stem cells in cryopreserved early preterm human cord blood samples","volume":"79","author":"Mirabelli","year":"2011","journal-title":"Cytom. A"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3900","DOI":"10.1111\/j.1742-4658.2008.06537.x","article-title":"KCTD5, a putative substrate adaptor for cullin3 ubiquitin ligases","volume":"275","author":"Trinidad","year":"2008","journal-title":"FEBS J."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Zhang, X., Zhu, L., Zhou, Y., Shi, A., Wang, H., Han, M., Wan, X., Kilonzo, S.B., Luo, X., and Chen, T. (2018). Interference with KCTD9 inhibits NK cell activation and ameliorates fulminant liver failure in mice. BMC Immunol., 19.","DOI":"10.1186\/s12865-018-0256-x"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Mirabelli, P., Coppola, L., and Salvatore, M. (2019). Cancer Cell Lines Are Useful Model Systems for Medical Research. Cancers, 11.","DOI":"10.3390\/cancers11081098"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"710","DOI":"10.4049\/jimmunol.148.3.710","article-title":"Regulation of expression of the leukocyte integrin CD11a (LFA-1) molecule during differentiation of HL-60 cells along the monocyte\/macrophage pathway","volume":"148","author":"Back","year":"1992","journal-title":"J. Immunol."},{"key":"ref_22","first-page":"700","article-title":"Granulocytic differentiation of human NB4 promyelocytic leukemia cells induced by all-trans retinoic acid metabolites","volume":"61","author":"Idres","year":"2001","journal-title":"Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0006-2952(00)00297-5","article-title":"Induction of erythroid differentiation of human K562 cells by cisplatin analogs","volume":"60","author":"Bianchi","year":"2000","journal-title":"Biochem. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.blre.2016.08.005","article-title":"Molecular biomarkers in acute myeloid leukemia","volume":"31","author":"Arroyave","year":"2017","journal-title":"Blood Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1111\/ejh.13172","article-title":"Clinical implications of molecular markers in acute myeloid leukemia","volume":"102","author":"Kayser","year":"2019","journal-title":"Eur. J. Haematol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/2045-3701-3-45","article-title":"The KCTD family of proteins: Structure, function, disease relevance","volume":"3","author":"Liu","year":"2013","journal-title":"Cell Biosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"U132","DOI":"10.1038\/ncb2013","article-title":"Histone deacetylase and Cullin3-RENKCTD11 ubiquitin ligase interplay regulates Hedgehog signalling through Gli acetylation","volume":"12","author":"Canettieri","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3109","DOI":"10.1093\/brain\/aww244","article-title":"Pathogenic variants in KCTD7 perturb neuronal K+ fluxes and glutamine transport","volume":"139","author":"Moen","year":"2016","journal-title":"Brain"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/nature11091","article-title":"KCTD13 is a major driver of mirrored neuroanatomical phenotypes of the 16p11.2 copy number variant","volume":"485","author":"Golzio","year":"2012","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.ajhg.2013.03.002","article-title":"Mutations in KCTD1 Cause Scalp-Ear-Nipple Syndrome","volume":"92","author":"Marneros","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"10519","DOI":"10.1038\/s41598-019-46911-4","article-title":"Molecular basis of the scalp-ear-nipple syndrome unraveled by the characterization of disease-causing KCTD1 mutants","volume":"9","author":"Smaldone","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Williams, M.J., Goergen, P., Rajendran, J., Zheleznyakova, G., Hagglund, M.G., Perland, E., Bagchi, S., Kalogeropoulou, A., Khan, Z., and Fredriksson, R. (2014). Obesity-Linked Homologues TfAP-2 and Twz Establish Meal Frequency in Drosophila melanogaster. PLoS Genet., 10.","DOI":"10.1371\/journal.pgen.1004499"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Smaldone, G., Pirone, L., Capolupo, A., Vitagliano, L., Monti, M.C., Di Gaetano, S., and Pedone, E. (2018). The essential player in adipogenesis GRP78 is a novel KCTD15 interactor. Inter. J. Biol. Macromol.","DOI":"10.1016\/j.ijbiomac.2018.04.078"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"158514","DOI":"10.1016\/j.bbalip.2019.08.010","article-title":"KCTD1: A novel modulator of adipogenesis through the interaction with the transcription factor AP2\u03b1","volume":"1864","author":"Pirone","year":"2019","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2870","DOI":"10.1073\/pnas.1300203110","article-title":"Inhibition of neural crest formation by Kctd15 involves regulation of transcription factor AP-2","volume":"110","author":"Zarelli","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/s41389-019-0175-6","article-title":"KCTD15 inhibits the Hedgehog pathway in Medulloblastoma cells by increasing protein levels of the oncosuppressor KCASH2","volume":"8","author":"Spiombi","year":"2019","journal-title":"Oncogenesis"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Smaldone, G., Pirone, L., Balasco, N., Di Gaetano, S., Pedone, E.M., and Vitagliano, L. (2015). Cullin 3 Recognition Is Not a Universal Property among KCTD Proteins. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0126808"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1002\/1873-3468.12203","article-title":"The BTB domains of the potassium channel tetramerization domain proteins prevalently assume pentameric states","volume":"590","author":"Smaldone","year":"2016","journal-title":"Febs Lett."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1186\/s12967-019-2125-7","article-title":"Purification of viable peripheral blood mononuclear cells for biobanking using a robotized liquid handling workstation","volume":"17","author":"Coppola","year":"2019","journal-title":"J. Transl. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2","DOI":"10.5334\/ojb.26","article-title":"SDN Biobank: Bioresource of Human Samples Associated with Functional and\/or Morphological Bioimaging Results for the Study of Oncological, Cardiological, Neurological, and Metabolic Diseases","volume":"4","author":"Mirabelli","year":"2017","journal-title":"Open J. Bioresour."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/10\/6\/371\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:35:34Z","timestamp":1760175334000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/10\/6\/371"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,4]]},"references-count":40,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["diagnostics10060371"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics10060371","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,4]]}}}