Artikel ; Online: Ponatinib and STAT5 Inhibitor Pimozide Combined Synergistic Treatment Applications Potentially Overcome Drug Resistance via Regulating the Cytokine Expressional Network in Chronic Myeloid Leukemia Cells.
2024 Band 44, Heft 4, Seite(n) 178–189
Abstract: Chronic myeloid leukemia (CML) is a clonal myeloproliferative hematological disease characterized by the chimeric breakpoint-cluster region/Abelson kinase1 (BCR::ABL1) oncoprotein; playing a pivotal role in CML molecular pathology, diagnosis, treatment, ... ...
| Abstract | Chronic myeloid leukemia (CML) is a clonal myeloproliferative hematological disease characterized by the chimeric breakpoint-cluster region/Abelson kinase1 (BCR::ABL1) oncoprotein; playing a pivotal role in CML molecular pathology, diagnosis, treatment, and possible resistance arising from the success and tolerance of tyrosine kinase inhibitor (TKI)-based therapy. The transcription factor STAT5 constitutive signaling, which is influenced by the cytokine signaling network, triggers BCR::ABL1-based CML pathogenesis and is also relevant to acquired TKI resistance. The unsuccessful therapeutic approaches targeting BCR::ABL1, in particular third-line therapy with ponatinib, still need to be further developed with alternative combination strategies to overcome drug resistance. As treatment with the STAT5 inhibitor pimozide in combination with ponatinib resulted in an efficient and synergistic therapeutic approach in TKI-resistant CML cells, this study focused on identifying the underlying amplification of ponatinib response mechanisms by determining different cytokine expression profiles in parental and ponatinib-resistant CML cells, |
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| Mesh-Begriff(e) | Humans ; Pimozide/pharmacology ; Pimozide/therapeutic use ; Cytokines/metabolism ; Drug Resistance, Neoplasm/genetics ; Fusion Proteins, bcr-abl/genetics ; Fusion Proteins, bcr-abl/metabolism ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; STAT5 Transcription Factor/genetics ; STAT5 Transcription Factor/metabolism ; Interleukin-15/metabolism ; Interleukin-15/therapeutic use ; Interleukin-6/metabolism ; Interleukin-9/metabolism ; Interleukin-9/therapeutic use ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology ; Imidazoles ; Pyridazines |
| Chemische Substanzen | ponatinib (4340891KFS) ; Pimozide (1HIZ4DL86F) ; Cytokines ; Fusion Proteins, bcr-abl (EC 2.7.10.2) ; Protein Kinase Inhibitors ; STAT5 Transcription Factor ; Interleukin-15 ; Interleukin-6 ; Interleukin-9 ; Imidazoles ; Pyridazines |
| Sprache | Englisch |
| Erscheinungsdatum | 2024-04-08 |
| Erscheinungsland | United States |
| Dokumenttyp | Journal Article |
| ZDB-ID | 1226675-9 |
| ISSN | 1557-7465 ; 1079-9907 |
| ISSN (online) | 1557-7465 |
| ISSN | 1079-9907 |
| DOI | 10.1089/jir.2023.0170 |
| Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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