Differential gene expression analysis of dasatinib-induced colitis in a patient with chronic myeloid leukemia followed for 3\xa0years: a case report

Naoki Oshima,Norihisa Ishimura,Yoshikazu Kinoshita,Masaya Inoue,Takahiro Okada,Kotaro Shibagaki,Ichiro Moriyama,Shunji Ishihara,Yoshiyuki Mishima,Junji Suzumiya,Kousaku Kawashima,Chie Onishi,Fumiyoshi Ikejiri

doi:10.1186/s12876-020-01584-6

Naoki Oshima, Norihisa Ishimura + Show 11 more

Open Access

https://doi.org/10.1186/s12876-020-01584-6

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Abstract

BackgroundDasatinib 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 presentationWe 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.ConclusionDasatinib induces immune-mediated colitis following lymphocyte infiltration.

Highlights

Dasatinib is a second-generation tyrosine kinase inhibitor (TKI) developed for treatment of patients with chronic myeloid leukemia (CML)
A recent study conducted in Japan revealed that 6 (33%) of 18 CML patients who received dasatinib developed hemorrhagic colitis without symptoms [12]
Hemorrhagic colitis is a unique adverse event that can occur during dasatinib treatment in CML patients and generally less common, though can be treated by stopping the drug administration [13]

Summary

Introduction

Dasatinib is a second-generation tyrosine kinase inhibitor (TKI) developed for treatment of patients with chronic myeloid leukemia (CML). A recent study conducted in Japan revealed that 6 (33%) of 18 CML patients who received dasatinib developed hemorrhagic colitis without symptoms [12]. We performed analysis of inflamed colonic mucosa gene expression to elucidate the details of colitis that develops in patients receiving dasatinib.

Results

Conclusion