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Nimesulide upregulated autophagy-associated genes and induced the first-in-human partial remission in acute myeloid leukemia.
A study published in Frontiers In Oncology portrayed the first-in-human acute myeloid leukemia (AML) partial response elicited by Nimesulide and depicted upregulation of autophagy-related genes following Nimesulide therapy both in vivo and in vitro. This study was conducted to provide the first-in-human clinical response to Nimesulide in AML, as well as insights into the mechanisms of action implicated in this impact using whole exome sequencing, cell culture, and transcriptome experiments.
Samples of peripheral blood and bone marrow were acquired from AML patient. The leukemic cell lines were grown in RPMI-1640 media. In the cellular tests, the medicines Nimesulide, Prednisolone, and Cytarabine were utilized. Flow Cytometry assays were carried out in treated cell lines to identify early and late apoptosis, followed by drug screening and cell viability studies. The RNA was extracted and sequenced. Flow cytometry experiments were done utilizing the ANOVA statistical test. This was followed by multiple comparisons with the aid of Tukey's test.
Characterization of clinical response was done via 82% reduction of bone marrow blasts linked with differentiation of myeloblasts and total clearance of peripheral blood blasts. In all the AML cell lines, Nimesulide was found to trigger in-vitro cell mortality and cell cycle arrest. From Nimesulide-treated cell lines of serial whole-transcriptome, the Weighted Correlation Network Analysis (WGCNA) data revealed that sets of genes upgraded after therapy with Nimesulide were enriched for genes linked with apoptosis and autophagy.
On the contrary, the downgraded sets of genes were related to RNA splicing and cell cycle. Serial transcriptome of the bone marrow validated the elevation of autophagy-related genes following Nimesulide response. Finally, it was evident that Nimesulide enhances the cytotoxic in vitro impact of various FDA-approved chemotherapeutic medications used in AML, including cytarabine. Hence, combining Nimesulide with anti-AML FDA-approved medicines promotes cell mortality in vitro, indicating a potential role for this medication in AML management.
Frontiers In Oncology
Molecular Characterization of a First-in-Human Clinical Response to Nimesulide in Acute Myeloid Leukemia
Victória Tomaz et al.
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