{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T01:42:42Z","timestamp":1787794962926,"version":"build-2784847793"},"reference-count":93,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Centre in Poland","award":["2022\/47\/O\/NZ5\/00288"],"award-info":[{"award-number":["2022\/47\/O\/NZ5\/00288"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Acute myeloid leukemia (AML) is an aggressive and often fatal hematopoietic malignancy, diagnosed predominantly in the elderly. The five-year survival of patients with AML is as low as 30%. Differentiation therapy of a subtype of AML, named acute promyelocytic leukemia (APL), using all-trans retinoic acid (ATRA) was the most successful example of a targeted therapy against AML. Epigenetic-based differentiation therapies for other subtypes of AML are also showing improvements in response and in survival rates. Thus, in this study, we investigated a potential differentiation therapy with a combination of 1,25-dihydroxyvitamin D (1,25D) analog (named PRI5202) and low concentration of Fludarabine. We show that such a combination elicits immunostimulatory and pro-differentiation effects in AML cells, specifically in those with activating mutations in fibroblast growth factor receptor (FGFR) and Janus kinase (JAK) pathways. We show here that both PRI5202 and Fludarabine are potent activators of the transcription of many innate immunity-related genes, and that, in combination, their effects are in many aspects synergistic. We propose that such a low-intensity regimen may be suitable for older patients with AML, who are unfit for intensive chemotherapy. We also present data indicating that PRI5202 induces myeloid differentiation in blasts from patients with myelodysplastic syndrome (MDS), and we propose to further investigate PRI5202 as a differentiation therapy for patients suffering from MDS.<\/jats:p>","DOI":"10.3390\/cells14231841","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T15:33:06Z","timestamp":1763739186000},"page":"1841","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Synergy in Immunostimulatory and Pro-Differentiation Effects of Vitamin D Analog and Fludarabine in Acute Myeloid Leukemias"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4311-041X","authenticated-orcid":false,"given":"Subhradeep","family":"Haldar","sequence":"first","affiliation":[{"name":"Department of Medical Biotechnology, Faculty of Biotechnology, University of Wroc\u0142aw, Joliot-Curie 14a, 50-383 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artem","family":"Petruk","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, Faculty of Biotechnology, University of Wroc\u0142aw, Joliot-Curie 14a, 50-383 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Marchwicka","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, Faculty of Biotechnology, University of Wroc\u0142aw, Joliot-Curie 14a, 50-383 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9518-4142","authenticated-orcid":false,"given":"Andrzej","family":"Kutner","sequence":"additional","affiliation":[{"name":"Department of Drug Chemistry, Pharmaceutical and Biomedical Analysis, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Biernat","sequence":"additional","affiliation":[{"name":"Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wroc\u0142aw Medical University, Pasteura 4, 50-367 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dariusz","family":"Wo\u0142owiec","sequence":"additional","affiliation":[{"name":"Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation, Wroc\u0142aw Medical University, Pasteura 4, 50-367 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6808-5464","authenticated-orcid":false,"given":"Ewa","family":"Marcinkowska","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, Faculty of Biotechnology, University of Wroc\u0142aw, Joliot-Curie 14a, 50-383 Wroc\u0142aw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.1016\/S0140-6736(23)00108-3","article-title":"Acute myeloid leukaemia","volume":"401","author":"DiNardo","year":"2023","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Huang, G., Cai, X., Liu, Y., Qian, B., and Li, D. (2024). Global, regional, and national burden of acute myeloid leukemia, 1990\u20132021: A systematic analysis for the global burden of disease study 2021. Biomark. Res., 12.","DOI":"10.1186\/s40364-024-00649-y"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Sackstein, P., Williams, A., Zemel, R., Marks, J.A., Renteria, A.S., and Rivero, G. (2024). Transplant Eligible and Ineligible Elderly Patients with AML\u2014A Genomic Approach and Next Generation Questions. Biomedicines, 12.","DOI":"10.3390\/biomedicines12050975"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1182\/blood.2019003988","article-title":"Molecular patterns of response and treatment failure after frontline venetoclax combinations in older patients with AML","volume":"135","author":"DiNardo","year":"2020","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Totiger, T.M., Ghoshal, A., Zabroski, J., Sondhi, A., Bucha, S., Jahn, J., Feng, Y., and Taylor, J. (2023). Targeted Therapy Development in Acute Myeloid Leukemia. Biomedicines, 11.","DOI":"10.3390\/biomedicines11020641"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.1182\/blood-2007-07-102798","article-title":"Acute promyelocytic leukemia: From highly fatal to highly curable","volume":"111","author":"Wang","year":"2008","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1111\/j.0954-6820.1957.tb00124.x","article-title":"Acute promyelocytic leukemia","volume":"159","author":"Hillestad","year":"1957","journal-title":"Acta Med Scand"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"142","DOI":"10.2991\/chi.k.210703.001","article-title":"History of Acute Promyelocytic Leukemia","volume":"3","author":"Sanz","year":"2021","journal-title":"Clin. Hematol. Int."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Iyer, S.G., Elias, L., Stanchina, M., and Watts, J. (2022). The treatment of acute promyelocytic leukemia in 2023: Paradigm, advances, and future directions. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.1062524"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/sj.cdd.4400673","article-title":"Retinoid-dependent growth inhibition, differentiation and apoptosis in acute promyelocytic leukemia cells. Expression and activation of caspases","volume":"7","author":"Gianni","year":"2000","journal-title":"Cell Death Differ."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Watts, J., Perez, A., Pereira, L., Fan, Y.-S., Brown, G., Vega, F., Petrie, K., Swords, R., and Zelent, A. (2017). A case of AML characterized by a novel t(4;15)(q31;q22) translocation that confers a growth-stimulatory response to retinoid-based therapy. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18071492"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1182\/blood.2024024009","article-title":"How I treat patients with AML using azacitidine and venetoclax","volume":"145","author":"Wei","year":"2025","journal-title":"Blood"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Liao, E. (2018). Vitamin D and leukaemia. Extraskeletal Effects of Vitamin D, Springer.","DOI":"10.1007\/978-3-319-73742-3"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"100406","DOI":"10.1016\/j.jlr.2023.100406","article-title":"Full-length nuclear receptor allosteric regulation","volume":"64","author":"Choi","year":"2023","journal-title":"J. Lipid Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e1424","DOI":"10.1210\/clinem\/dgad289","article-title":"Paricalcitol and Extended-Release Calcifediol for Treatment of Secondary Hyperparathyroidism in Non-Dialysis Chronic Kidney Disease: Results From a Network Meta-Analysis","volume":"108","author":"Franchi","year":"2023","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5696","DOI":"10.5826\/dpc.1503a5696","article-title":"Patient Satisfaction with Calcipotriol\/Betamethasone Dipropionate Cream in Psoriatic Patients Previously Treated With Foam Vehicle","volume":"15","author":"Caldarola","year":"2025","journal-title":"Dermatol. Pr. Concept."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Marcinkowska, E. (2022). Vitamin D Derivatives in Acute Myeloid Leukemia: The Matter of Selecting the Right Targets. Nutrients, 14.","DOI":"10.3390\/nu14142851"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Marchwicka, A., Corcoran, A., Berkowska, K., and Marcinkowska, E. (2016). Restored expression of vitamin D receptor and sensitivity to 1,25-dihydroxyvitamin D3 in response to disrupted fusion FOP2-FGFR1 gene in acute myeloid leukemia cells. Cell Biosci., 6.","DOI":"10.1186\/s13578-016-0075-9"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1016\/j.cellsig.2011.06.010","article-title":"The driver of malignancy in KG-1a leukemic cells, FGFR1OP2\u2013FGFR1, encodes an HSP90 addicted oncoprotein","volume":"23","author":"Jin","year":"2011","journal-title":"Cell. Signal."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Marchwicka, A., Nowak, U., Grembowska, A., Jakuszak, A., Por\u0119ba, P., and Marcinkowska, E. (2022). Overexpressed fibroblast growth factor receptors increase 1,25-dihydroxyvitamin D-dependent differentiation of acute myeloid leukemia cells. J. Steroid Biochem. Mol. Biol., 224.","DOI":"10.1016\/j.jsbmb.2022.106173"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Sabatier, M., Boet, E., Zaghdoudi, S., Guiraud, N., Hucteau, A., Polley, N., Cognet, G., Saland, E., Lauture, L., and Farge, T. (2021). Activation of Vitamin D Receptor Pathway Enhances Differentiating Capacity in Acute Myeloid Leukemia with Isocitrate Dehydrogenase Mutations. Cancers, 13.","DOI":"10.20944\/preprints202108.0529.v1"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Marchwicka, A., Nowak, K., Satyr, A., Wo\u0142owiec, D., and Marcinkowska, E. (2023). Immuno-Stimulating Activity of 1,25-Dihydroxyvitamin D in Blood Cells from Five Healthy People and in Blasts from Five Patients with Leukemias and Pre-Leukemic States. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076504"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"100032","DOI":"10.1016\/j.pharmr.2024.100032","article-title":"Vitamin D and its analogs in immune system regulation","volume":"77","author":"Artusa","year":"2025","journal-title":"Pharmacol. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Hanel, A., and Carlberg, C. (2022). Time-Resolved Gene Expression Analysis Monitors the Regulation of Inflammatory Mediators and Attenuation of Adaptive Immune Response by Vitamin D. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23020911"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Fasouli, E.S., and Katsantoni, E. (2021). JAK-STAT in Early Hematopoiesis and Leukemia. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.669363"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"111652","DOI":"10.1016\/j.cellsig.2025.111652","article-title":"STAT1 inhibition promotes oxidative stress to sustain leukemia stem cell maintenance","volume":"130","author":"Han","year":"2025","journal-title":"Cell. Signal."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Moser, B., Edtmayer, S., Witalisz-Siepracka, A., and Stoiber, D. (2021). The Ups and Downs of STAT Inhibition in Acute Myeloid Leukemia. Biomedicines, 9.","DOI":"10.3390\/biomedicines9081051"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.3390\/molecules14031183","article-title":"Current Status of Older and New Purine Nucleoside Analogues in the Treatment of Lymphoproliferative Diseases","volume":"14","author":"Robak","year":"2009","journal-title":"Molecules"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1111\/ejh.14370","article-title":"Comparison of HiDAC Versus FLAG-IDA in the Treatment of Relapsed Acute Myeloid Leukemia and High-Risk Myelodysplastic Syndrome","volume":"114","author":"Tang","year":"2025","journal-title":"Eur. J. Haematol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1007\/s00277-005-1090-9","article-title":"FLAG-IDA in the treatment of refractory\/relapsed adult acute lymphoblastic leukemia","volume":"84","author":"Specchia","year":"2005","journal-title":"Ann. Hematol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.beha.2017.10.001","article-title":"How can one optimize induction therapy in AML?","volume":"30","author":"Luger","year":"2017","journal-title":"Best Pract. Res. Clin. Haematol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Suh, H.C., Rowley, S.D., Kaur, S., Lukasik, B., McKiernan, P., Boonstra, M., Baker, M., DiLorenzo, M., Skarbnik, A., and Voss, J. (2025). Prospective, Randomized, Comparative Study of Myeloablative Fludarabine\/Busulfan and Fludarabine\/Busulfan\/Total Body Irradiation Conditioning in Myeloid Diseases. Cancers, 17.","DOI":"10.3390\/cancers17071140"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3016","DOI":"10.1182\/blood-2010-08-304683","article-title":"Fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy is highly effective treatment for relapsed patients with CLL","volume":"117","author":"Badoux","year":"2011","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Lin, J., Qi, W., Chen, K., Yan, Y., Li, X., Feng, Z., and Pan, X. (2019). Downregulating STAT1\/caspase-3 signaling with fludarabine to alleviate progression in a rat model of steroid-induced avascular necrosis of the femoral head. J. Biochem. Mol. Toxicol., 33.","DOI":"10.1002\/jbt.22265"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1038\/s41423-021-00698-5","article-title":"Fludarabine inhibits type I interferon-induced expression of the SARS-CoV-2 receptor angiotensin-converting enzyme 2","volume":"18","author":"Xiu","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.jsbmb.2015.09.033","article-title":"Biological evaluation of new vitamin D2 analogues","volume":"164","author":"Corcoran","year":"2016","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_37","first-page":"166","article-title":"Dimethyl fumarate and vitamin D derivatives cooperatively enhance VDR and Nrf2 signaling in differentiating AML cells in vitro and inhibit leukemia progression in a xenograft mouse model","volume":"187","author":"Nachliely","year":"2019","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Piatek, K., Kutner, A., Cacsire Castillo-Tong, D., Manhardt, T., Kupper, N., Nowak, U., Chody\u0144ski, M., Marcinkowska, E., Kallay, E., and Schepelmann, M. (2021). Vitamin D Analogs Regulate the Vitamin D System and Cell Viability in Ovarian Cancer Cells. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010172"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Biernatowska, A., W\u00f3jtowicz, K., Trombik, T., Sikorski, A.F., and Czogalla, A. (2022). MPP1 Determines the Mobility of Flotillins and Controls the Confinement of Raft-Associated Molecules. Cells, 11.","DOI":"10.3390\/cells11030311"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Singh, V., Kirtipal, N., Song, B., and Lee, S. (2024). Normalization of RNA-Seq data using adaptive trimmed mean with multi-reference. Brief. Bioinform., 25.","DOI":"10.1093\/bib\/bbae241"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.jsbmb.2012.07.001","article-title":"Opposite regulation of vitamin D receptor by ATRA in AML cells susceptible and resistant to vitamin D-induced differentiation","volume":"132","author":"Gocek","year":"2012","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.cell.2010.12.032","article-title":"Reference Maps of Human ES and iPS Cell Variation Enable High-Throughput Characterization of Pluripotent Cell Lines","volume":"144","author":"Bock","year":"2011","journal-title":"Cell"},{"key":"ref_43","unstructured":"Oliveros, J.C., and Venny, C. (2025, November 13). An Interactive Tool for Comparing Lists with Venn\u2019s Diagrams. 2007\u20132015. Available online: https:\/\/bioinfogp.cnb.csic.es\/tools\/venny\/index.html."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1093\/bioinformatics\/btz931","article-title":"ShinyGO: A graphical gene-set enrichment tool for animals and plants","volume":"36","author":"Ge","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"pl1","DOI":"10.1126\/scisignal.2004088","article-title":"Integrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the cBioPortal","volume":"6","author":"Gao","year":"2013","journal-title":"Sci. Signal."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3861","DOI":"10.1158\/0008-5472.CAN-23-0816","article-title":"Analysis and Visualization of Longitudinal Genomic and Clinical Data from the AACR Project GENIE Biopharma Collaborative in cBioPortal","volume":"83","author":"Kundra","year":"2023","journal-title":"Cancer Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"450","DOI":"10.3324\/haematol.2010.033191","article-title":"The JAK2 V617F somatic mutation, mortality and cancer risk in the general population","volume":"96","author":"Nielsen","year":"2011","journal-title":"Haematologica"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Gou, P., Zhang, W., and Giraudier, S. (2022). Insights into the Potential Mechanisms of JAK2V617F Somatic Mutation Contributing Distinct Phenotypes in Myeloproliferative Neoplasms. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031013"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"W98","DOI":"10.1093\/nar\/gkx247","article-title":"GEPIA: A web server for cancer and normal gene expression profiling and interactive analyses","volume":"45","author":"Tang","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"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_51","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/ng.2653","article-title":"The Genotype-Tissue Expression (GTEx) project","volume":"45","author":"Lonsdale","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_52","first-page":"11","article-title":"Regulation of Leukemic Cell Differentiation through the Vitamin D Receptor at the Levels of Intracellular Signal Transduction, Gene Transcription, and Protein Trafficking and Stability","volume":"2012","author":"Gocek","year":"2012","journal-title":"Leuk. Res. Treat."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1002\/ijc.2910170504","article-title":"Establishment and characterization of a human histiocytic lymphoma cell line (U-937)","volume":"17","author":"Nilsson","year":"1976","journal-title":"Int. J. Cancer"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5907","DOI":"10.1073\/pnas.80.19.5907","article-title":"Induction of monocytic differentiation and bone resorption by 1,25-dihydroxyvitamin D3","volume":"80","author":"Teitelbaum","year":"1983","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"100110","DOI":"10.1016\/j.crphar.2022.100110","article-title":"Evaluation of synergism in drug combinations and reference models for future orientations in oncology","volume":"3","author":"Duarte","year":"2022","journal-title":"Curr. Res. Pharmacol. Drug Discov."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1182\/blood-2009-03-209262","article-title":"The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: Rationale and important changes","volume":"114","author":"Vardiman","year":"2009","journal-title":"Blood"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0145-2126(83)90057-7","article-title":"1,25-Dihydroxyvitamin D3 inhibits proliferation of human promyelocytic leukaemia (HL60) cells and induces monocyte-macrophage differentiation in HL60 and normal bone marrow cells","volume":"7","author":"McCarthy","year":"1983","journal-title":"Leuk. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/298679a0","article-title":"Amplification of Endogenous Myc-Related DNA Sequences in a Human Myeloid Leukaemia Cell Line","volume":"298","author":"Collins","year":"1982","journal-title":"Nature"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1073\/pnas.82.3.790","article-title":"Major deletions in the gene encoding the p53 tumor antigen cause lack of p53 expression in HL-60 cells","volume":"82","author":"Wolf","year":"1985","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"9155","DOI":"10.1093\/nar\/12.23.9155","article-title":"Three different mutations in codon 61 of the human N-ras gene detected by synthetic oligonucleotide hybridization","volume":"12","author":"Bos","year":"1984","journal-title":"Nucleic Acids Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1126\/science.6177045","article-title":"HEL Cells: A New Human Erythroleukemia Cell Line with Spontaneous and Induced Globin Expression","volume":"216","author":"Martin","year":"1982","journal-title":"Science"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1172\/JCI112593","article-title":"Vitamin D compounds. Effect on clonal proliferation and differentiation of human myeloid cells","volume":"78","author":"Munker","year":"1986","journal-title":"J. Clin. Invest."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Ge, S.X., Son, E.W., and Yao, R. (2018). iDEP: An integrated web application for differential expression and pathway analysis of RNA-Seq data. BMC Bioinform., 19.","DOI":"10.1186\/s12859-018-2486-6"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"iyad031","DOI":"10.1093\/genetics\/iyad031","article-title":"The Gene Ontology knowledgebase in 2023","volume":"224","author":"Consortium","year":"2023","journal-title":"Genetics"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1194\/jlr.R031534","article-title":"Cytochrome P450-mediated metabolism of vitamin D","volume":"55","author":"Jones","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.abb.2011.11.003","article-title":"25-Hydroxyvitamin D-24-hydroxylase (CYP24A1): Its important role in the degradation of vitamin D","volume":"523","author":"Jones","year":"2012","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1111\/imm.13634","article-title":"Role of CD14 in human disease","volume":"169","author":"Sharygin","year":"2023","journal-title":"Immunology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1126\/science.1698311","article-title":"CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein","volume":"249","author":"Wright","year":"1990","journal-title":"Science"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1182\/blood.V73.1.284.284","article-title":"Monocyte antigen CD14 is a phospholipid anchored membrane protein","volume":"73","author":"Simmons","year":"1989","journal-title":"Blood"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1038\/icb.2010.145","article-title":"SLAM (CD150) is a multitasking immunoreceptor: From cosignalling to bacterial recognition","volume":"89","author":"Sintes","year":"2011","journal-title":"Immunol. Cell Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1080\/21505594.2021.1879471","article-title":"TREM1 regulates antifungal immune responses in invasive pulmonary aspergillosis","volume":"12","author":"Cunha","year":"2021","journal-title":"Virulence"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"6209","DOI":"10.2174\/1381612822666160826110539","article-title":"Therapeutic Potential of Targeting TREM-1 in Inflammatory Diseases and Cancer","volume":"22","author":"Bosco","year":"2016","journal-title":"Curr. Pharm. Des."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1080\/15548627.2015.1075110","article-title":"Phenylbutyrate induces LL-37-dependent autophagy and intracellular killing of Mycobacterium tuberculosis in human macrophages","volume":"11","author":"Rekha","year":"2015","journal-title":"Autophagy"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Ren, S., Shen, J., Cheng, A., Lu, L., Chan, R., Li, Z., Wang, X., Wong, C., Zhang, L., and Ng, S. (2013). FK-16 derived from the anticancer peptide LL-37 induces caspase-independent apoptosis and autophagic cell death in colon cancer cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063641"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"5576","DOI":"10.1016\/S0021-9258(18)45611-6","article-title":"Isolation and characterization of the receptor on human neutrophils that mediates cellular adherence","volume":"262","author":"Hickstein","year":"1987","journal-title":"J. Biol. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1038\/s41467-018-04013-1","article-title":"The molecular basis of JAK\/STAT inhibition by SOCS1","volume":"9","author":"Liau","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.4161\/epi.29941","article-title":"RASA4 undergoes DNA hypermethylation in resistant juvenile myelomonocytic leukemia","volume":"9","author":"Poetsch","year":"2014","journal-title":"Epigenetics"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3118","DOI":"10.1038\/emboj.2012.167","article-title":"GPCR activation of Ras and PI3Kc in neutrophils depends on PLCb2\/b3 and the RasGEF RasGRP4","volume":"31","author":"Suire","year":"2012","journal-title":"EMBO J."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e2002162118","DOI":"10.1073\/pnas.2002162118","article-title":"Ras inhibitor CAPRI enables neutrophil-like cells to chemotax through a higher-concentration range of gradients","volume":"118","author":"Xu","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1016\/j.steroids.2008.06.010","article-title":"Side-chain modified vitamin D analogs induce rapid accumulation of VDR in the cell nuclei proportionately to their differentiation-inducing potential","volume":"73","author":"Gocek","year":"2008","journal-title":"Steroids"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1016\/j.febslet.2007.03.055","article-title":"Activation of intracellular signaling pathways is necessary for an increase in VDR expression and its nuclear translocation","volume":"581","author":"Gocek","year":"2007","journal-title":"FEBS Lett."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Gaikwad, S., Gonz\u00e1lez, C.M., Vilari\u00f1o, D., Lasanta, G., Villaverde, C., Mouri\u00f1o, A., Verlinden, L., Verstuyf, A., Peluso-Iltis, C., and Rochel, N. (2021). Lithocholic acid-based design of noncalcemic vitamin D receptor agonists. Bioorg. Chem., 111.","DOI":"10.1016\/j.bioorg.2021.104878"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1182\/blood-2018-08-868752","article-title":"Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia","volume":"133","author":"DiNardo","year":"2019","journal-title":"Blood"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1038\/7445","article-title":"Fludarabine-induced immunosuppression is associated with inhibition of STAT1 signaling","volume":"5","author":"Frank","year":"1999","journal-title":"Nat. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1016\/j.hoc.2006.06.007","article-title":"Purine Analogues: Rationale for Development, Mechanisms of Action, and Pharmacokinetics in Hairy Cell Leukemia","volume":"20","author":"Juliusson","year":"2006","journal-title":"Hematol.\/Oncol. Clin."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Straube, J., Lane, S.W., and Vu, T. (2021). Optimizing DNA hypomethylating therapy in acute myeloid leukemia and myelodysplastic syndromes. Bioessays, 43.","DOI":"10.1002\/bies.202100125"},{"key":"ref_87","first-page":"2636","article-title":"Studies in mouse L-cells on the incorporation of 1-beta-D-arabinofuranosylcytosine into DNA and on inhibition of DNA polymerase by 1-beta-D-arabinofuranosylcytosine 5\u2032-triphosphate","volume":"30","author":"Graham","year":"1970","journal-title":"Cancer Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2166","DOI":"10.1021\/acs.biochem.7b00208","article-title":"DNA Methyltransferases Demonstrate Reduced Activity against Arabinosylcytosine: Implications for Epigenetic Instability in Acute Myeloid Leukemia","volume":"56","author":"Nabel","year":"2017","journal-title":"Biochemistry"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/0065-2571(94)00008-Q","article-title":"Thiopurine induced disturbance of DNA methylation in human malignant cells","volume":"35","author":"Lambooy","year":"1995","journal-title":"Adv. Enzym. Regul."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1517\/13543780903071038","article-title":"Cladribine: Not just another purine analogue?","volume":"18","author":"Spurgeon","year":"2009","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Si, H., Wang, J., He, R., Yu, X., Li, S., Huang, J., Li, J., Tang, X., Song, X., and Tu, Z. (2021). Identification of U937JAK3-M511I Acute Myeloid Leukemia Cells as a Sensitive Model to JAK3 Inhibitor. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.807200"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"49733","DOI":"10.18632\/oncotarget.10438","article-title":"SCLLTargeting FGFR1 to suppress leukemogenesis in syndromic and de novo AML in murine models","volume":"7","author":"Wu","year":"2016","journal-title":"Oncotarget"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"3309","DOI":"10.1038\/sj.onc.1203650","article-title":"Transformation and Stat activation by derivatives of FGFR1, FGFR3, and FGFR4","volume":"19","author":"Hart","year":"2000","journal-title":"Oncogene"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/23\/1841\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T05:30:52Z","timestamp":1764048652000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/23\/1841"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,21]]},"references-count":93,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["cells14231841"],"URL":"https:\/\/doi.org\/10.3390\/cells14231841","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,21]]}}}