{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T04:10:11Z","timestamp":1771647011724,"version":"3.50.1"},"reference-count":87,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T00:00:00Z","timestamp":1657756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Professorinnenprogramm Universit\u00e4t Rostock","award":["GHS-15-0019"],"award-info":[{"award-number":["GHS-15-0019"]}]},{"name":"the European Union","award":["GHS-15-0019"],"award-info":[{"award-number":["GHS-15-0019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Little is known about optimally applying chemotherapeutic agents in a specific temporal sequence to rapidly reduce the tumor load and to improve therapeutic efficacy. The clinical optimization of drug efficacy while reducing side effects is still restricted due to an incomplete understanding of the mode of action and related tumor relapse mechanisms on the molecular level. The molecular characterization of transcriptomic drug signatures can help to identify the affected pathways, downstream regulated genes and regulatory interactions related to tumor relapse in response to drug application. We tried to outline the dynamic regulatory reprogramming leading to tumor relapse in relapsed MLL-rearranged pro-B-cell acute lymphoblastic leukemia (B-ALL) cells in response to two first-line treatments: dexamethasone (Dexa) and cytarabine (AraC). We performed an integrative molecular analysis of whole transcriptome profiles of each treatment, specifically considering public knowledge of miRNA regulation via a network-based approach to unravel key driver genes and miRNAs that may control the relapse mechanisms accompanying each treatment. Our results gave hints to the crucial regulatory roles of genes leading to Dexa-resistance and related miRNAs linked to chemosensitivity. These genes and miRNAs should be further investigated in preclinical models to obtain more hints about relapse processes.<\/jats:p>","DOI":"10.3390\/genes13071240","type":"journal-article","created":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T00:17:10Z","timestamp":1657844230000},"page":"1240","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Molecular Characterization of the Response to Conventional Chemotherapeutics in Pro-B-ALL Cell Lines in Terms of Tumor Relapse"],"prefix":"10.3390","volume":"13","author":[{"given":"Yvonne Saara","family":"Gladbach","sequence":"first","affiliation":[{"name":"Institute for Biostatistics and Informatics in Medicine and Ageing Research (IBIMA), Rostock University Medical Center, 18057 Rostock, Germany"},{"name":"Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany"},{"name":"Division of Applied Bioinformatics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa-Madeleine","family":"Sklarz","sequence":"additional","affiliation":[{"name":"Clinic III\u2014Hematology, Oncology, Palliative Medicine, Center for Internal Medicine, Rostock University Medical Center, 18057 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catrin","family":"Roolf","sequence":"additional","affiliation":[{"name":"Clinic III\u2014Hematology, Oncology, Palliative Medicine, Center for Internal Medicine, Rostock University Medical Center, 18057 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Beck","sequence":"additional","affiliation":[{"name":"Chronix Biomedical GmbH, 37073 G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekkehard","family":"Sch\u00fctz","sequence":"additional","affiliation":[{"name":"Chronix Biomedical GmbH, 37073 G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georg","family":"Fuellen","sequence":"additional","affiliation":[{"name":"Institute for Biostatistics and Informatics in Medicine and Ageing Research (IBIMA), Rostock University Medical Center, 18057 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Junghanss","sequence":"additional","affiliation":[{"name":"Clinic III\u2014Hematology, Oncology, Palliative Medicine, Center for Internal Medicine, Rostock University Medical Center, 18057 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7123-7986","authenticated-orcid":false,"given":"Hugo","family":"Murua Escobar","sequence":"additional","affiliation":[{"name":"Clinic III\u2014Hematology, Oncology, Palliative Medicine, Center for Internal Medicine, Rostock University Medical Center, 18057 Rostock, Germany"},{"name":"Comprehensive Cancer Center Mecklenburg-Vorpommern (CCC-MV), Campus Rostock, Rostock University Medical Center, 18057 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9102-8839","authenticated-orcid":false,"given":"Mohamed","family":"Hamed","sequence":"additional","affiliation":[{"name":"Institute for Biostatistics and Informatics in Medicine and Ageing Research (IBIMA), Rostock University Medical Center, 18057 Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1053\/j.seminhematol.2008.09.003","article-title":"Treatment of Adult Acute Lymphoblastic Leukemia","volume":"46","author":"Hoelzer","year":"2009","journal-title":"Semin. Hematol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.blre.2011.08.001","article-title":"Chemoimmunotherapy in acute lymphoblastic leukemia","volume":"26","author":"Hoelzer","year":"2012","journal-title":"Blood Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1182\/asheducation-2016.1.573","article-title":"Treatment of older patients with acute lymphoblastic leukemia","volume":"2016","year":"2016","journal-title":"Hematology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"E147","DOI":"10.1188\/16.CJON.E147-E154","article-title":"Adult Acute Lymphoblastic Leukemia: A Genetic Overview and Application to Clinical Practice","volume":"20","author":"Jacobson","year":"2016","journal-title":"Clin. J. Oncol. Nurs."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3688","DOI":"10.1182\/blood-2015-01-567842","article-title":"Rationale for targeting the pre\u2013B-cell receptor signaling pathway in acute lymphoblastic leukemia","volume":"125","year":"2015","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s13046-016-0333-z","article-title":"High expression of ID family and IGJ genes signature as predictor of low induction treatment response and worst survival in adult Hispanic patients with B-acute lymphoblastic leukemia","volume":"35","author":"Combita","year":"2016","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1016\/S0140-6736(12)62187-4","article-title":"Acute lymphoblastic leukaemia","volume":"381","author":"Inaba","year":"2013","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1038\/nrd4204","article-title":"PI3K and cancer: Lessons, challenges and opportunities","volume":"13","author":"Fruman","year":"2014","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4","DOI":"10.3389\/fped.2017.00004","article-title":"MLL-Rearranged Leukemias\u2014An Update on Science and Clinical Approaches","volume":"5","author":"Winters","year":"2017","journal-title":"Front. Pediatrics"},{"key":"ref_10","first-page":"761","article-title":"Chemical genomic screening identifies LY294002 as a modulator of glucocorticoid resistance in MLL-rearranged infant ALL","volume":"28","author":"Schneider","year":"2013","journal-title":"Leukemia"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"v69","DOI":"10.1093\/annonc\/mdw025","article-title":"Acute lymphoblastic leukaemia in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"27","author":"Hoelzer","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.bbmt.2016.12.639","article-title":"Next-Generation Sequencing in Adult B Cell Acute Lymphoblastic Leukemia Patients","volume":"23","author":"Torra","year":"2017","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_13","first-page":"29","article-title":"Advances in biology of acute lymphoblastic leukemia (ALL) and therapeutic implications","volume":"8","author":"Mohseni","year":"2018","journal-title":"Am. J. Blood Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e577","DOI":"10.1038\/bcj.2017.53","article-title":"Acute lymphoblastic leukemia: A comprehensive review and 2017 update","volume":"7","author":"Terwilliger","year":"2017","journal-title":"Blood Cancer J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12935-020-01431-4","article-title":"Combination of the PI3K inhibitor idelalisib with the conventional cytostatics cytarabine and dexamethasone leads to pathway modulations inducing anti-proliferative effects in B lymphoblastic leukaemia cell lines","volume":"20","author":"Sklarz","year":"2020","journal-title":"Cancer Cell Int."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2938","DOI":"10.1200\/JCO.2014.59.1636","article-title":"Childhood Acute Lymphoblastic Leukemia: Progress through Collaboration","volume":"33","author":"Pui","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1111\/j.1365-2141.2005.05509.x","article-title":"Benefit of dexamethasone compared with prednisolone for childhood acute lymphoblastic leukaemia: Results of the UK Medical Research Council ALL97 randomized trial","volume":"129","author":"Mitchell","year":"2005","journal-title":"Br. J. Haematol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1200\/JCO.2012.43.2070","article-title":"Postinduction Dexamethasone and Individualized Dosing of Escherichia Coli L-Asparaginase Each Improve Outcome of Children and Adolescents With Newly Diagnosed Acute Lymphoblastic Leukemia: Results From a Randomized Study\u2014Dana-Farber Cancer Institute ALL Consortium Protocol 00-01","volume":"31","author":"Vrooman","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1016\/S1470-2045(10)70114-5","article-title":"Glucocorticoid use in acute lymphoblastic leukaemia","volume":"11","author":"Inaba","year":"2010","journal-title":"Lancet Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Berger, D.P., Engelhardt, R., and Mertelsmann, R. (2017). Das Rote Buch-H\u00e4matologische und Internistische Onkologie. Das Rote Buch-H\u00e4matologische und Internistische Onkologie, Ecomed-Storck GmbH. [6th ed.].","DOI":"10.1007\/978-3-662-51420-7"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1053\/j.seminhematol.2008.09.007","article-title":"Treatment of Childhood Acute Lymphoblastic Leukemia","volume":"46","author":"Stanulla","year":"2009","journal-title":"Semin. Hematol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11864-016-0393-5","article-title":"Obesity and Metabolic Syndrome Among Adult Survivors of Childhood Leukemia","volume":"17","author":"Gibson","year":"2016","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41419-018-0625-7","article-title":"Metabolic reprogramming of acute lymphoblastic leukemia cells in response to glucocorticoid treatment","volume":"9","author":"Dyczynski","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3781","DOI":"10.1182\/blood.V124.21.3781.3781","article-title":"T Cell Exhaustion and Downregulation of Cytotoxic NK Cells\u2014An Immune Escape Mechanism in Adult Acute Lymphoblastic Leukemia","volume":"124","author":"Brissot","year":"2014","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e1207","DOI":"10.1002\/cnr2.1207","article-title":"The RS4;11 cell line as a model for leukaemia with t(4;11)(q21;q23): Revised characterisation of cytogenetic features","volume":"2","author":"Ragusa","year":"2019","journal-title":"Cancer Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5201","DOI":"10.1182\/blood-2012-01-401687","article-title":"Epigenetic reprogramming reverses the relapse-specific gene expression signature and restores chemosensitivity in childhood B-lymphoblastic leukemia","volume":"119","author":"Bhatla","year":"2012","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1016\/j.ejca.2015.06.117","article-title":"The potential of clofarabine in MLL -rearranged infant acute lymphoblastic leukaemia","volume":"51","author":"Stumpel","year":"2015","journal-title":"Eur. J. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2898","DOI":"10.1038\/s41375-020-0895-9","article-title":"Preclinical efficacy of gemcitabine in MLL-rearranged infant acute lymphoblastic leukemia","volume":"34","author":"Wander","year":"2020","journal-title":"Leukemia"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1038\/leu.2015.359","article-title":"Tumor suppressor IKZF1 mediates glucocorticoid resistance in B-cell precursor acute lymphoblastic leukemia","volume":"30","author":"Marke","year":"2015","journal-title":"Leukemia"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3000","DOI":"10.1182\/blood-2017-02-766204","article-title":"Suppression of B-cell development genes is key to glucocorticoid efficacy in treatment of acute lymphoblastic leukemia","volume":"129","author":"Kruth","year":"2017","journal-title":"Blood"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1158\/1078-0432.CCR-15-0114","article-title":"Modulation of Glucocorticoid Resistance in Pediatric T-cell Acute Lymphoblastic Leukemia by Increasing BIM Expression with the PI3K\/mTOR Inhibitor BEZ235","volume":"22","author":"Hall","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_32","unstructured":"Andrews, S., Krueger, F., Segonds-Pichon, A., Biggins, L., Krueger, C., and Wingett, S. (2020, March 01). FastQC: A Quality Control Tool for High Throughput Sequence Data. Available online: http:\/\/www.bioinformatics.babraham.ac.uk\/projects\/."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"R36","DOI":"10.1186\/gb-2013-14-4-r36","article-title":"TopHat2: Accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions","volume":"14","author":"Kim","year":"2013","journal-title":"Genome Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq\u2014A Python framework to work with high-throughput sequencing data","volume":"31","author":"Anders","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_37","unstructured":"Carlson, M. (2015). org.Hs.eg.db: Genome wide annotation for Human. R Package Version, 312."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Hamed, M., Trumm, J., Spaniol, C., Sethi, R., Irhimeh, M.R., Fuellen, G., Paulsen, M., and Helms, V. (2017). Linking Hematopoietic Differentiation to Co-Expressed Sets of Pluripotency-Associated and Imprinted Genes and to Regulatory microRNA-Transcription Factor Motifs. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0166852"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"W283","DOI":"10.1093\/nar\/gkv418","article-title":"TFmiR: A web server for constructing and analyzing disease-specific transcription factor and miRNA co-regulatory networks","volume":"43","author":"Hamed","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1186\/1471-2105-11-419","article-title":"TAM: A method for enrichment and depletion analysis of a microRNA category in a list of microRNAs","volume":"11","author":"Lu","year":"2010","journal-title":"BMC Bioinform."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"W180","DOI":"10.1093\/nar\/gky509","article-title":"TAM 2.0: Tool for MicroRNA set analysis","volume":"46","author":"Li","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Nazarieh, M., Wiese, A., Will, T., Hamed, M., and Helms, V. (2016). Identification of key player genes in gene regulatory networks. BMC Syst. Biol., 10.","DOI":"10.1186\/s12918-016-0329-5"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1093\/bioinformatics\/btq675","article-title":"Cytoscape 2.8: New features for data integration and network visualization","volume":"27","author":"Smoot","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1093\/bioinformatics\/btq064","article-title":"GOSemSim: An R package for measuring semantic similarity among GO terms and gene products","volume":"26","author":"Yu","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"106","DOI":"10.3389\/fimmu.2017.00106","article-title":"Mesenchymal Stem Cells Support Survival and Proliferation of Primary Human Acute Myeloid Leukemia Cells through Heterogeneous Molecular Mechanisms","volume":"8","author":"Brenner","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/s41375-018-0373-9","article-title":"Mesenchymal stem cells in suppression or progression of hematologic malignancy: Current status and challenges","volume":"33","author":"Lee","year":"2019","journal-title":"Leukemia"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.bbamcr.2015.08.015","article-title":"Advances in understanding the acute lymphoblastic leukemia bone marrow microenvironment: From biology to therapeutic targeting","volume":"1863","author":"Chiarini","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.ccell.2015.05.003","article-title":"CXCR4 is required for leukemia-initiating cell activity in T cell acute ymphoblastic leukemia","volume":"27","author":"Passaro","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.3324\/haematol.2009.018580","article-title":"Dexamethasone compared to prednisolone for adults with acute lymphoblastic leukemia or lymphoblastic lymphoma: Final results of the ALL-4 randomized, phase III trial of the EORTC Leukemia Group","volume":"95","author":"LaBar","year":"2010","journal-title":"Haematologica"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Molina-Pinelo, S., Carnero, A., Rivera, F., Estevez-Garcia, P., Bozada, J.M., Limon, M.L., Benavent, M., G\u00f3mez, J., Pastor, M.D., and Chaves, M. (2014). MiR-107 and miR-99a-3p predict chemotherapy response in patients with advanced colorectal cancer. BMC Cancer, 14.","DOI":"10.1186\/1471-2407-14-656"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.canlet.2014.07.026","article-title":"MicroRNA-370 suppresses proliferation and promotes endometrioid ovarian cancer chemosensitivity to cDDP by negatively regulating ENG","volume":"353","author":"Chen","year":"2014","journal-title":"Cancer Lett."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1038\/leu.2014.302","article-title":"A microRNA-mediated regulatory loop modulates NOTCH and MYC oncogenic signals in B- and T-cell malignancies","volume":"29","author":"Ortega","year":"2015","journal-title":"Leukemia"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1136\/gut.2008.175497","article-title":"Survival prediction of gastric cancer by a seven-microRNA signature","volume":"59","author":"Li","year":"2010","journal-title":"Gut"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"15945","DOI":"10.1038\/s41598-017-16112-y","article-title":"Overexpression of suppressive microRNAs, miR-30a and miR-200c are associated with improved survival of breast cancer patients","volume":"7","author":"Kawaguchi","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1053\/j.gastro.2019.01.261","article-title":"Biomarkers Associated With Response to Regorafenib in Patients With Hepatocellular Carcinoma","volume":"156","author":"Teufel","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2514","DOI":"10.12659\/MSM.894372","article-title":"Downregulation of MiR-30a is Associated with Poor Prognosis in Lung Cancer","volume":"21","author":"Tang","year":"2015","journal-title":"Med. Sci. Monit."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-Rivas, L.G., Jerez, J.M., Carmona, R., De Luque, V., Vicioso, L., Claros, M.G., Viguera, E., Pajares, B., S\u00e1nchez, A., and Ribelles, N. (2014). A microRNA Signature Associated with Early Recurrence in Breast Cancer. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0091884"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/s41419-019-1326-6","article-title":"miR-30a regulates cancer cell response to chemotherapy through SNAI1\/IRS1\/AKT pathway","volume":"10","author":"Wang","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Forno, I., Ferrero, S., Russo, M.V., Gazzano, G., Giangiobbe, S., Montanari, E., Del Nero, A., Rocco, B.M.C., Albo, G., and Languino, L.R. (2015). Deregulation of MiR-34b\/Sox2 Predicts Prostate Cancer Progression. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0130060"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s13046-019-1059-5","article-title":"MicroRNA-34 family: A potential tumor suppressor and therapeutic candidate in cancer","volume":"38","author":"Zhang","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Edmonds, M.D., and Eischen, C.M. (2014). Differences in miRNA Expression in Early Stage Lung Adenocarcinomas that Did and Did Not Relapse. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0101802"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s12943-016-0518-2","article-title":"Clinical significance of microRNAs in chronic and acute human leukemia","volume":"15","author":"Yeh","year":"2016","journal-title":"Mol. Cancer"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4443","DOI":"10.1158\/0008-5472.CAN-08-4025","article-title":"Epigenetic silencing of the tumor suppressor microRNA Hsa-miR-124a regulates CDK6 expression and confers a poor prognosis in acute lymphoblastic leukemia","volume":"69","author":"Agirre","year":"2009","journal-title":"Cancer Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"78","DOI":"10.3109\/10428194.2013.790023","article-title":"Overexpression ofMIR9indicates poor prognosis in acute lymphoblastic leukemia","volume":"55","author":"Sugita","year":"2013","journal-title":"Leuk. Lymphoma"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.jsbmb.2017.05.014","article-title":"MiR-124 contributes to glucocorticoid resistance in acute lymphoblastic leukemia by promoting proliferation, inhibiting apoptosis and targeting the glucocorticoid receptor","volume":"172","author":"Liang","year":"2017","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1111\/cas.12766","article-title":"Potential roles of microRNA-29a in the molecular pathophysiology of T-cell acute lymphoblastic leukemia","volume":"106","author":"Oliveira","year":"2015","journal-title":"Cancer Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"5330","DOI":"10.1182\/blood.V124.21.5330.5330","article-title":"High Expression of Mir-15a Predicts Shorter Survival and Worse Response to Chemotherapy in Patients with Acute Myeloid Leukemia (AML)","volume":"124","author":"Butrym","year":"2014","journal-title":"Blood"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4761","DOI":"10.1182\/blood-2009-07-192740","article-title":"Chronic lymphocytic leukemia: Interplay between noncoding RNAs and protein-coding genes","volume":"114","author":"Calin","year":"2009","journal-title":"Blood"},{"key":"ref_71","first-page":"8797","article-title":"MiR-410 regulates malignant biological behavior of pediatric acute lymphoblastic leukemia through targeting FKBP5 and Akt signaling pathway","volume":"22","author":"Qi","year":"2018","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s40169-019-0240-y","article-title":"Let-7as biomarker, prognostic indicator, and therapy for precision medicine in cancer","volume":"8","author":"Chirshev","year":"2019","journal-title":"Clin. Transl. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3233","DOI":"10.2147\/OTT.S126819","article-title":"Targeted regulation of miR-98 on E2F1 increases chemosensitivity of leukemia cells K562\/A02","volume":"10","author":"Huang","year":"2017","journal-title":"OncoTargets Ther."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"10494","DOI":"10.1073\/pnas.1902375116","article-title":"Heterogeneity in refractory acute myeloid leukemia","volume":"116","author":"Horibata","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BSR20200097","article-title":"High expression of AK1 predicts inferior prognosis in acute myeloid leukemia patients undergoing chemotherapy","volume":"40","author":"Qin","year":"2020","journal-title":"Biosci. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1111\/ijlh.12284","article-title":"Prognostic significance ofMSI2predicts unfavorable outcome in adult B-acute lymphoblastic leukemia","volume":"37","author":"Aly","year":"2014","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"150","DOI":"10.4149\/neo_2016_018","article-title":"Prognostic significance of the Musashi-2 (MSI2) gene in childhood acute lymphoblastic leukemia","volume":"63","author":"Zhao","year":"2016","journal-title":"Neoplasma"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s13045-019-0722-9","article-title":"Differential roles of STAT1 and STAT2 in the sensitivity of JAK2V617F- vs. BCR-ABL-positive cells to interferon alpha","volume":"12","author":"Schubert","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"E2039","DOI":"10.1073\/pnas.1600557113","article-title":"Regulation of normal B-cell differentiation and malignant B-cell survival by OCT2","volume":"113","author":"Hodson","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"606","DOI":"10.3109\/10428191003592735","article-title":"OCT-2 expression and OCT-2\/BOB.1 co-expression predict prognosis in patients with newly diagnosed acute myeloid leukemia","volume":"51","author":"Advani","year":"2010","journal-title":"Leuk. Lymphoma"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Sailo, B.L., Banik, K., Girisa, S., Bordoloi, D., Fan, L., Halim, C.E., Wang, H., Kumar, A.P., Zheng, D., and Mao, X. (2019). FBXW7 in Cancer: What Has Been Unraveled Thus Far?. Cancers, 11.","DOI":"10.3390\/cancers11020246"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"74779","DOI":"10.18632\/oncotarget.11340","article-title":"Exocytosis of polyubiquitinated proteins in bortezomib-resistant leukemia cells: A role for MARCKS in acquired resistance to proteasome inhibitors","volume":"7","author":"Franke","year":"2016","journal-title":"Oncotarget"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/leu.2014.255","article-title":"Targeting phospho-MARCKS overcomes drug-resistance and induces antitumor activity in preclinical models of multiple myeloma","volume":"29","author":"Yang","year":"2015","journal-title":"Leukemia"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.3389\/fonc.2019.01046","article-title":"Two Receptors, Two Isoforms, Two Cancers: Comprehensive Analysis of KIT and TrkA Expression in Neuroblastoma and Acute Myeloid Leukemia","volume":"9","author":"Lebedev","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1007\/s10555-017-9699-4","article-title":"(Immuno)proteasomes as therapeutic target in acute leukemia","volume":"36","author":"Cloos","year":"2017","journal-title":"Cancer Metastasis Rev."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1872","DOI":"10.1182\/blood-2011-10-382861","article-title":"Gene expression profiles predictive of outcome and age in infant acute lymphoblastic leukemia: A Children\u2019s Oncology Group study","volume":"119","author":"Kang","year":"2012","journal-title":"Blood"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1111\/jcmm.13436","article-title":"Combination of arsenic trioxide and Dasatinib: A new strategy to treat Philadelphia chromosome-positive acute lymphoblastic leukaemia","volume":"22","author":"Wang","year":"2017","journal-title":"J. Cell. Mol. Med."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/7\/1240\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:50:04Z","timestamp":1760140204000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/7\/1240"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,14]]},"references-count":87,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["genes13071240"],"URL":"https:\/\/doi.org\/10.3390\/genes13071240","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,14]]}}}