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Molecular Characterization of a First-in-Human Clinical Response to Nimesulide in Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a hematologic malignancy associated with high morbidity and mortality. Here we describe a case of a patient with AML who presented a partial response after utilization of the non-steroidal anti-inflammatory drug nimesulide. The response was characterized by complete c...

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Autores principales: Tomaz, Victória, Griesi-Oliveira, Karina, Puga, Renato D., Conti, Bruno J., Santos, Fabio P. S., Hamerschlak, Nelson, Campregher, Paulo V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9215211/
https://www.ncbi.nlm.nih.gov/pubmed/35756679
http://dx.doi.org/10.3389/fonc.2022.874168
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author Tomaz, Victória
Griesi-Oliveira, Karina
Puga, Renato D.
Conti, Bruno J.
Santos, Fabio P. S.
Hamerschlak, Nelson
Campregher, Paulo V.
author_facet Tomaz, Victória
Griesi-Oliveira, Karina
Puga, Renato D.
Conti, Bruno J.
Santos, Fabio P. S.
Hamerschlak, Nelson
Campregher, Paulo V.
author_sort Tomaz, Victória
collection PubMed
description Acute myeloid leukemia (AML) is a hematologic malignancy associated with high morbidity and mortality. Here we describe a case of a patient with AML who presented a partial response after utilization of the non-steroidal anti-inflammatory drug nimesulide. The response was characterized by complete clearance of peripheral blood blasts and an 82% decrease of bone marrow blasts associated with myeloblast differentiation. We have then shown that nimesulide induces in vitro cell death and cell cycle arrest in all AML cell lines (HL-60, THP-1, OCI-AML2, and OCI-AML3). Weighted Correlation Network Analysis (WGCNA) of serial whole-transcriptome data of cell lines treated with nimesulide revealed that the sets of genes upregulated after treatment with nimesulide were enriched for genes associated with autophagy and apoptosis, and on the other hand, the sets of downregulated genes were associated with cell cycle and RNA splicing. Serial transcriptome of bone marrow patient sample confirmed the upregulation of genes associated with autophagy after the response to nimesulide. Lastly, we demonstrated that nimesulide potentiates the cytotoxic in vitro effect of several Food and Drug Administration (FDA)-approved chemotherapy drugs used in AML, including cytarabine.
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spelling pubmed-92152112022-06-23 Molecular Characterization of a First-in-Human Clinical Response to Nimesulide in Acute Myeloid Leukemia Tomaz, Victória Griesi-Oliveira, Karina Puga, Renato D. Conti, Bruno J. Santos, Fabio P. S. Hamerschlak, Nelson Campregher, Paulo V. Front Oncol Oncology Acute myeloid leukemia (AML) is a hematologic malignancy associated with high morbidity and mortality. Here we describe a case of a patient with AML who presented a partial response after utilization of the non-steroidal anti-inflammatory drug nimesulide. The response was characterized by complete clearance of peripheral blood blasts and an 82% decrease of bone marrow blasts associated with myeloblast differentiation. We have then shown that nimesulide induces in vitro cell death and cell cycle arrest in all AML cell lines (HL-60, THP-1, OCI-AML2, and OCI-AML3). Weighted Correlation Network Analysis (WGCNA) of serial whole-transcriptome data of cell lines treated with nimesulide revealed that the sets of genes upregulated after treatment with nimesulide were enriched for genes associated with autophagy and apoptosis, and on the other hand, the sets of downregulated genes were associated with cell cycle and RNA splicing. Serial transcriptome of bone marrow patient sample confirmed the upregulation of genes associated with autophagy after the response to nimesulide. Lastly, we demonstrated that nimesulide potentiates the cytotoxic in vitro effect of several Food and Drug Administration (FDA)-approved chemotherapy drugs used in AML, including cytarabine. Frontiers Media S.A. 2022-06-08 /pmc/articles/PMC9215211/ /pubmed/35756679 http://dx.doi.org/10.3389/fonc.2022.874168 Text en Copyright © 2022 Tomaz, Griesi-Oliveira, Puga, Conti, Santos, Hamerschlak and Campregher https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Tomaz, Victória
Griesi-Oliveira, Karina
Puga, Renato D.
Conti, Bruno J.
Santos, Fabio P. S.
Hamerschlak, Nelson
Campregher, Paulo V.
Molecular Characterization of a First-in-Human Clinical Response to Nimesulide in Acute Myeloid Leukemia
title Molecular Characterization of a First-in-Human Clinical Response to Nimesulide in Acute Myeloid Leukemia
title_full Molecular Characterization of a First-in-Human Clinical Response to Nimesulide in Acute Myeloid Leukemia
title_fullStr Molecular Characterization of a First-in-Human Clinical Response to Nimesulide in Acute Myeloid Leukemia
title_full_unstemmed Molecular Characterization of a First-in-Human Clinical Response to Nimesulide in Acute Myeloid Leukemia
title_short Molecular Characterization of a First-in-Human Clinical Response to Nimesulide in Acute Myeloid Leukemia
title_sort molecular characterization of a first-in-human clinical response to nimesulide in acute myeloid leukemia
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9215211/
https://www.ncbi.nlm.nih.gov/pubmed/35756679
http://dx.doi.org/10.3389/fonc.2022.874168
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