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Glycogen synthase kinase 3 beta/CCR6-positive bone marrow cells correlate with disease activity in multicentric Castleman disease-TAFRO

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Title: Glycogen synthase kinase 3 beta/CCR6-positive bone marrow cells correlate with disease activity in multicentric Castleman disease-TAFRO
Authors: Abe, Nobuya Browse this author
Kono, Michihito Browse this author →KAKEN DB
Kono, Michihiro Browse this author
Ohnishi, Naoki Browse this author
Sato, Tomoya Browse this author
Tarumi, Masato Browse this author
Yoshimura, Masaru Browse this author
Sato, Taiki Browse this author
Karino, Kohei Browse this author
Shimizu, Yuka Browse this author
Fujieda, Yuichiro Browse this author
Kato, Masaru Browse this author
Hasebe, Rie Browse this author
Oku, Kenji Browse this author
Murakami, Masaaki Browse this author →KAKEN DB
Atsumi, Tatsuya Browse this author →KAKEN DB
Keywords: multicentric Castleman disease-TAFRO
lymphoproliferative disorders
chemokine
bone marrow
glycogen synthase 3
Issue Date: Mar-2022
Publisher: John Wiley & Sons
Journal Title: British journal of haematology
Volume: 196
Issue: 5
Start Page: 1194
End Page: 1204
Publisher DOI: 10.1111/bjh.17993
Abstract: Multicentric Castleman disease-thrombocytopenia, anasarca, reticulin fibrosis of bone marrow, renal dysfunction and organomegaly (MCD-TAFRO)-is an emergent phenotype characterized by lymphoproliferation, fluid collection, hemocytopenia and multiple organopathy. Although studies have demonstrated an aberrant blood cytokine/chemokine profile referred to as "chemokine storm", the pathogenesis remains unclear. We aimed to identify pathogenic key molecules, potential diagnostic targets and therapeutic markers in MCD-TAFRO using serum cytokine/chemokine profiles. We performed the targeted cytokine/chemokine multiplex analysis in six cases of MCD-TAFRO with remission or non-remission status. We observed significant changes in serum concentrations of CCL2, CCL5, and Chitinase-3-like-1 in the MCD-TAFRO patients with active state compared to inactive state. Ingenuity pathway analysis revealed that glycogen synthase kinase 3 (GSK3) and CCR6, which is expressed in megakaryocytes, were detected as upstream positive regulators for activating MCD-TAFRO status. More GSK3 beta(+)CCR6(+) cells like megakaryocytes were detected in the bone marrow of patients with MCD-TAFRO than in those with systemic lupus erythematosus, MCD-not otherwise specified or autoimmune haemophagocytic lymphohistiocytosis. The cellularity of GSK3 beta(+)CCR6(+) cells was correlated with disease activity, including thrombocytopenia and anaemia. In conclusion, GSK3 beta and CCR6 of bone marrow cells were potentially involved in the pathogenesis of MCD-TAFRO and may act as diagnostic targets and therapeutic markers.
Rights: Abe, N., Kono, M., Kono, M., Ohnishi, N., Sato, T., Tarumi, M., Yoshimura, M., Sato, T., Karino, K., Shimizu, Y., Fujieda, Y., Kato, M., Hasebe, R., Oku, K., Murakami, M. and Atsumi, T. (2022), Glycogen synthase kinase 3β/CCR6-positive bone marrow cells correlate with disease activity in multicentric Castleman disease-TAFRO. Br J Haematol, 196: 1194-1204,which has been published in final form at 10.1111/bjh.17993. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving (http://olabout.wiley.com/WileyCDA/Section/id-828039.html).
Type: article (author version)
URI: http://hdl.handle.net/2115/88234
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 河野 通仁

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