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Differential gene expression analysis of dasatinib-induced colitis in a patient with chronic myeloid leukemia followed for 3 years: a case report

BACKGROUND: Dasatinib is a second-generation tyrosine kinase inhibitor (TKI) developed for treatment of patients with chronic myeloid leukemia (CML). The drug has been shown to act as a potent multikinase inhibitor by blocking not only the BCR-ABL1 gene sequence but also the SRC kinase family, thoug...

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Autores principales: Oshima, Naoki, Mishima, Yoshiyuki, Shibagaki, Kotaro, Kawashima, Kousaku, Ishimura, Norihisa, Ikejiri, Fumiyoshi, Onishi, Chie, Okada, Takahiro, Inoue, Masaya, Moriyama, Ichiro, Suzumiya, Junji, Kinoshita, Yoshikazu, Ishihara, Shunji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789270/
https://www.ncbi.nlm.nih.gov/pubmed/33407162
http://dx.doi.org/10.1186/s12876-020-01584-6
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author Oshima, Naoki
Mishima, Yoshiyuki
Shibagaki, Kotaro
Kawashima, Kousaku
Ishimura, Norihisa
Ikejiri, Fumiyoshi
Onishi, Chie
Okada, Takahiro
Inoue, Masaya
Moriyama, Ichiro
Suzumiya, Junji
Kinoshita, Yoshikazu
Ishihara, Shunji
author_facet Oshima, Naoki
Mishima, Yoshiyuki
Shibagaki, Kotaro
Kawashima, Kousaku
Ishimura, Norihisa
Ikejiri, Fumiyoshi
Onishi, Chie
Okada, Takahiro
Inoue, Masaya
Moriyama, Ichiro
Suzumiya, Junji
Kinoshita, Yoshikazu
Ishihara, Shunji
author_sort Oshima, Naoki
collection PubMed
description BACKGROUND: Dasatinib is a second-generation tyrosine kinase inhibitor (TKI) developed for treatment of patients with chronic myeloid leukemia (CML). The drug has been shown to act as a potent multikinase inhibitor by blocking not only the BCR-ABL1 gene sequence but also the SRC kinase family, though unexpected adverse events such as pleural effusion have recently been reported in patients undergoing treatment with dasatinib. Hemorrhagic colitis is a unique gastrointestinal adverse events associated with dasatinib and its pathogenesis remains poorly understood. CASE PRESENTATION: We report here a case of dasatinib-induced asymptomatic colitis in a patient with CML, who showed no exacerbation in careful observations and maintained deep molecular response (DMR) during a 3-year period. In addition, we performed transcriptome analysis of inflamed colonic mucosa specimens to clarify the possible mechanism of colitis that develops in association with dasatinib administration. Our results demonstrated that differential gene expression, especially lymphocyte-associated genes and chemokines, is substantially involved in inflammation of colonic mucosa in affected patients. CONCLUSION: Dasatinib induces immune-mediated colitis following lymphocyte infiltration.
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spelling pubmed-77892702021-01-07 Differential gene expression analysis of dasatinib-induced colitis in a patient with chronic myeloid leukemia followed for 3 years: a case report Oshima, Naoki Mishima, Yoshiyuki Shibagaki, Kotaro Kawashima, Kousaku Ishimura, Norihisa Ikejiri, Fumiyoshi Onishi, Chie Okada, Takahiro Inoue, Masaya Moriyama, Ichiro Suzumiya, Junji Kinoshita, Yoshikazu Ishihara, Shunji BMC Gastroenterol Case Report BACKGROUND: Dasatinib is a second-generation tyrosine kinase inhibitor (TKI) developed for treatment of patients with chronic myeloid leukemia (CML). The drug has been shown to act as a potent multikinase inhibitor by blocking not only the BCR-ABL1 gene sequence but also the SRC kinase family, though unexpected adverse events such as pleural effusion have recently been reported in patients undergoing treatment with dasatinib. Hemorrhagic colitis is a unique gastrointestinal adverse events associated with dasatinib and its pathogenesis remains poorly understood. CASE PRESENTATION: We report here a case of dasatinib-induced asymptomatic colitis in a patient with CML, who showed no exacerbation in careful observations and maintained deep molecular response (DMR) during a 3-year period. In addition, we performed transcriptome analysis of inflamed colonic mucosa specimens to clarify the possible mechanism of colitis that develops in association with dasatinib administration. Our results demonstrated that differential gene expression, especially lymphocyte-associated genes and chemokines, is substantially involved in inflammation of colonic mucosa in affected patients. CONCLUSION: Dasatinib induces immune-mediated colitis following lymphocyte infiltration. BioMed Central 2021-01-06 /pmc/articles/PMC7789270/ /pubmed/33407162 http://dx.doi.org/10.1186/s12876-020-01584-6 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Case Report
Oshima, Naoki
Mishima, Yoshiyuki
Shibagaki, Kotaro
Kawashima, Kousaku
Ishimura, Norihisa
Ikejiri, Fumiyoshi
Onishi, Chie
Okada, Takahiro
Inoue, Masaya
Moriyama, Ichiro
Suzumiya, Junji
Kinoshita, Yoshikazu
Ishihara, Shunji
Differential gene expression analysis of dasatinib-induced colitis in a patient with chronic myeloid leukemia followed for 3 years: a case report
title Differential gene expression analysis of dasatinib-induced colitis in a patient with chronic myeloid leukemia followed for 3 years: a case report
title_full Differential gene expression analysis of dasatinib-induced colitis in a patient with chronic myeloid leukemia followed for 3 years: a case report
title_fullStr Differential gene expression analysis of dasatinib-induced colitis in a patient with chronic myeloid leukemia followed for 3 years: a case report
title_full_unstemmed Differential gene expression analysis of dasatinib-induced colitis in a patient with chronic myeloid leukemia followed for 3 years: a case report
title_short Differential gene expression analysis of dasatinib-induced colitis in a patient with chronic myeloid leukemia followed for 3 years: a case report
title_sort differential gene expression analysis of dasatinib-induced colitis in a patient with chronic myeloid leukemia followed for 3 years: a case report
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789270/
https://www.ncbi.nlm.nih.gov/pubmed/33407162
http://dx.doi.org/10.1186/s12876-020-01584-6
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