{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Novikova S"],"funding":["Russian Science Foundation"],"pagination":["4618"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11083274"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["25(9)"],"pubmed_abstract":["Combining new therapeutics with all-<i>trans</i>-retinoic acid (ATRA) could improve the efficiency of acute myeloid leukemia (AML) treatment. Modeling the process of ATRA-induced differentiation based on the transcriptomic profile of leukemic cells resulted in the identification of key targets that can be used to increase the therapeutic effect of ATRA. The genome-scale transcriptome analysis revealed the early molecular response to the ATRA treatment of HL-60 cells. In this study, we performed the transcriptomic profiling of HL-60, NB4, and K562 cells exposed to ATRA for 3-72 h. After treatment with ATRA for 3, 12, 24, and 72 h, we found 222, 391, 359, and 1032 differentially expressed genes (DEGs) in HL-60 cells, as well as 641, 1037, 1011, and 1499 DEGs in NB4 cells. We also found 538 and 119 DEGs in K562 cells treated with ATRA for 24 h and 72 h, respectively. Based on experimental transcriptomic data, we performed hierarchical modeling and determined cyclin-dependent kinase 6 (CDK6), tumor necrosis factor alpha (TNF-alpha), and transcriptional repressor CUX1 as the key regulators of the molecular response to the ATRA treatment in HL-60, NB4, and K562 cell lines, respectively. Mapping the data of TMT-based mass-spectrometric profiling on the modeling schemes, we determined CDK6 expression at the proteome level and its down-regulation at the transcriptome and proteome levels in cells treated with ATRA for 72 h. The combination of therapy with a CDK6 inhibitor (palbociclib) and ATRA (tretinoin) could be an alternative approach for the treatment of acute myeloid leukemia (AML)."],"journal":["International journal of molecular sciences"],"pubmed_title":["Systems Biology for Drug Target Discovery in Acute Myeloid Leukemia."],"pmcid":["PMC11083274"],"funding_grant_id":["21-74-20122"],"pubmed_authors":["Kurbatov L","Farafonova T","Tikhonova O","Soloveva N","Novikova S","Tolstova T","Zgoda V","Rusanov A"],"additional_accession":[]},"is_claimable":false,"name":"Systems Biology for Drug Target Discovery in Acute Myeloid Leukemia.","description":"Combining new therapeutics with all-<i>trans</i>-retinoic acid (ATRA) could improve the efficiency of acute myeloid leukemia (AML) treatment. Modeling the process of ATRA-induced differentiation based on the transcriptomic profile of leukemic cells resulted in the identification of key targets that can be used to increase the therapeutic effect of ATRA. The genome-scale transcriptome analysis revealed the early molecular response to the ATRA treatment of HL-60 cells. In this study, we performed the transcriptomic profiling of HL-60, NB4, and K562 cells exposed to ATRA for 3-72 h. After treatment with ATRA for 3, 12, 24, and 72 h, we found 222, 391, 359, and 1032 differentially expressed genes (DEGs) in HL-60 cells, as well as 641, 1037, 1011, and 1499 DEGs in NB4 cells. We also found 538 and 119 DEGs in K562 cells treated with ATRA for 24 h and 72 h, respectively. Based on experimental transcriptomic data, we performed hierarchical modeling and determined cyclin-dependent kinase 6 (CDK6), tumor necrosis factor alpha (TNF-alpha), and transcriptional repressor CUX1 as the key regulators of the molecular response to the ATRA treatment in HL-60, NB4, and K562 cell lines, respectively. Mapping the data of TMT-based mass-spectrometric profiling on the modeling schemes, we determined CDK6 expression at the proteome level and its down-regulation at the transcriptome and proteome levels in cells treated with ATRA for 72 h. The combination of therapy with a CDK6 inhibitor (palbociclib) and ATRA (tretinoin) could be an alternative approach for the treatment of acute myeloid leukemia (AML).","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Apr","modification":"2026-04-08T19:50:39.724Z","creation":"2026-04-08T14:31:27.536Z"},"accession":"S-EPMC11083274","cross_references":{"pubmed":["38731835"],"doi":["10.3390/ijms25094618"]}}