Faculty Profiles - FUJII Nobuharu

MISC - FUJII Nobuharu

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Single-Cell DNA Sequencing Reveals Cell-Level Genetic Evolutionary Processes and Clonal Structure in B-Cell Lymphomas

Hiroyuki Murakami, Ryota Chijimatsu, Hideki Ujiie, Yusuke Naoi, Kazutaka Sunami, Kazuhiko Yamamoto, Soichiro Fujii, Tomofumi Yano, Keisuke Seike, Hideaki Fujiwara, Noboru Asada, Nobuharu Fujii, Ken-ichi Matsuoka, Tomohiro Urata, Kazuhiro Ikeuchi, Hiroki Kobayashi, Yasuharu Sato, Shuta Tomida, Yoshinobu Maeda, Daisuke Ennishi

BLOOD 144 1368 - 1369 2024.11

Dynamic Shifts in Inflammation and Fibrotic Remodeling in Post-HSCT Bronchiolitis Obliterans: A Spatial Transcriptomics Study

Akira Yamamoto, Nobuharu Fujii, Keisuke Seike, Seiichiro Sugimoto, Yusuke Naoi, Yui Kambara, Kanako Fujiwara, Toshiki Terao, Tadashi Oyama, Mari Kunihiro, Takumi Kondo, Hiroki Kobayashi, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Keiko Fujii, Shinichi Toyooka, Yoshinobu Maeda

Blood 2024.11

Language：English

<jats:sec>
<jats:title/>
<jats:p>Bronchiolitis obliterans (BO) is a severe complication following hematopoietic stem cell transplantation (HSCT), significantly impacting patients' prognosis and quality of life. Despite its clinical importance, the underlying pathophysiological mechanisms remain poorly understood.</jats:p>
<jats:p>We analyzed lung specimens from three patients who developed BO post-HSCT and subsequently underwent lung transplantation. All patients had acute lymphoblastic leukemia as their primary disease and developed BO 1-2 years after HSCT. Healthy lung regions from two cancer patients served as controls. Using NanoString GeoMx Digital Spatial Profiling, we performed transcriptional profiling with the Human Whole Transcriptome Atlas on 94 regions of interest (ROIs). BO lesions were classified based on our previously established staging system (Kuroi T et al. Int J Hematol. 2021) and analyzed for both inner and outer bronchiolar regions.</jats:p>
<jats:p>Linear mixed model analysis identified significant differential gene expression between BO and control groups. GO enrichment analysis highlighted biological processes such as phagocytosis, positive regulation of leukocyte activation, and cell activation, indicating a close association with immune cells, particularly macrophages, which are known to obstruct bronchioles in BO. Processes such as regulation of cell-cell adhesion and post-Golgi vesicle-mediated transport were also enriched, suggesting involvement in extracellular matrix remodeling and fibroblast activation. GSEA further identified significant processes, including inflammatory response, defense response, positive regulation of response to stimulus, and vesicle-mediated transport. These results suggest an interplay between immune response and tissue remodeling. Notably, changes in the expression of genes such as HES1, IGF2BP2, PTPRF, and ITGB2, which are involved in cell adhesion and cytoskeletal reorganization, were closely associated with fibroblast activation and macrophage infiltration. These findings parallel the fibrosis process observed in BO following lung transplantation, where macrophage infiltration and myofibroblast activation are critical. Given these insights, our focus shifted to the dynamics of macrophages and myofibroblasts, aiming to understand their roles in the progression from inflammation to tissue remodeling.</jats:p>
<jats:p>CD68, a pan-macrophage marker, showed higher expression in Early and Middle-outside stages (Inflammatory Phase) of BO, but significantly decreased in Middle-inside and Late stages (Remodeling Phase) as the disease progressed. Unsupervised clustering analysis revealed distinct gene expression profiles between these phases, suggesting a temporal shift in disease mechanisms as BO progresses from inner bronchioles outwards. Correlation analysis revealed significant associations between CD68 and JAK1/STAT1 expression, as well as genes associated with myofibroblast activity and extracellular matrix remodeling (e.g., ACTA2, TGFB1). These findings suggest a coordinated process of inflammation and remodeling in BO, potentially involving the JAK-STAT pathway.</jats:p>
<jats:p>Linear mixed model analysis revealed distinct gene expression patterns between Inflammatory and Remodeling Phases, characterized by inflammatory/proliferation-related genes (e.g., CXCL6, HLA-family) and tissue remodeling/protein synthesis and genes (e.g., ITGB1, RPL and RPS families), respectively. This transition aligns with changes in macrophage-related gene expression. Pathway analysis revealed enrichment of translation, ribosomal activity, and metabolic processes in the Remodeling Phase, indicating a dynamic shift in biological activities as BO progresses.</jats:p>
<jats:p>In conclusion, this study reveals a transition in BO pathology from inflammation to remodeling, with macrophages playing a central role. The coordinated changes in gene expression provide a comprehensive picture of BO progression. These insights into post-HSCT BO pathophysiology highlight potential therapeutic targets in macrophage function and tissue remodeling pathways, suggesting possibilities for stage-specific interventions in BO treatment.</jats:p>
</jats:sec>

DOI： 10.1182/blood-2024-202251

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ネララビン関連重症神経障害単一施設での同種造血幹細胞移植にまつわる4症例

藤原加奈子, 藤原英晃, 久保田紗矢, 上田弥生, 林野健太, 近藤歌穂, 松原千哲, 寺尾俊紀, 木村真衣子, 清家圭介, 淺田騰, 西森久和, 藤井敬子, 藤井伸治, 松岡賢市, 前田嘉信

日本血液学会学術集会 85回 1268 - 1268 2023.10

ベネトクラクス,アザシチジンを含む化学療法後に初回同種造血幹移植を施行した急性骨髄性白血病の治療成績

松原千哲, 藤原英晃, 林野健太, 近藤歌穂, 藤原加奈子, 寺尾俊紀, 植田裕子, 松村彰文, 大山矩史, 鴨井千尋, 村上裕之, 守山喬史, 近藤匠, 清家圭介, 淺田騰, 遠西大輔, 西森久和, 藤井敬子, 藤井伸治, 松岡賢市, 前田嘉信

日本血液学会学術集会 85回 1250 - 1250 2023.10

臍帯血移植後にHTLV-1感染T細胞の多クローン性増殖を伴って発症した肺合併症に対し抗CCR4抗体が著効した1例

松原千哲, 松岡賢市, 近藤歌穂, 藤原加奈子, 寺尾俊紀, 植田裕子, 松村彰文, 守山喬史, 村上裕之, 近藤匠, 清家圭介, 藤原英晃, 淺田騰, 遠西大輔, 西森久和, 藤井敬子, 藤井伸治, 前田嘉信

臨床血液 64 ( 6 ) 563 - 563 2023.6

臍帯血移植後にHTLV-1感染T細胞の多クローン性増殖を伴って発症した肺合併症に対しCCR4抗体が著効した一例

松原千哲, 松岡賢市, 近藤歌穂, 藤原加奈子, 寺尾俊紀, 植田裕子, 松村彰文, 守山喬史, 村上裕之, 近藤匠, 清家圭介, 藤原英晃, 淺田騰, 遠西大輔, 西森久和, 藤井敬子, 藤井伸治, 中島誠, 中島誠, 内丸薫, 前田嘉信

日本血液学会学術集会抄録(Web) 85th 656 - 656 2023

Tisagenlecleucelのためのリンパ球採取-末梢血CD3⁺数と採取効率による処理量決定とロングアフェレーシスでの工夫-

藤井敬子, 阿部将也, 住居優一, 谷勝真, 浦田知宏, 高木尚江, 閘結稀, 池田亮, 浅野尚美, 小郷博昭, 北村亘, 清家圭介, 大塚文男, 藤井伸治, 藤井敬子, 阿部将也, 住居優一, 谷勝真, 浦田知宏, 高木尚江, 北村亘, 清家圭介, 大塚文男, 藤井伸治

日本輸血細胞治療学会誌 69 ( 2 ) 2023

Clinical significance of gynecological examinations in LTFU

鴨井千尋, 鴨井千尋, 藤井伸治, 藤井伸治, 松岡敬典, 藤原英晃, 淺田騰, 遠西大輔, 西森久和, 藤井敬子, 藤井敬子, 松岡賢市, 前田嘉信

日本造血・免疫細胞療法学会総会プログラム・抄録集 44th 2022

Analysis of cryopreserved unrelated donor bone marrow transplantation under the COVID-19 pandemic

松村彰文, 藤原英晃, 植田裕子, 守山喬史, 村上裕之, 住井優一, 浦田知宏, 木村真衣子, 近藤匠, 浅田騰, 遠西大輔, 西森久和, 松岡賢市, 藤井敬子, 藤井伸治, 鴨井千尋, 前田嘉信

日本造血・免疫細胞療法学会総会プログラム・抄録集 44th 2022

Modification of post-transplant cyclophosphamide and tacrolimus in haploidentical transplantation

寺尾俊紀, 松岡賢市, 近藤匠, 高須賀裕樹, 鴨井千尋, 植田裕子, 松村彰文, 松原千哲, 近藤歌穂, 藤原英晃, 淺田騰, 遠西大輔, 西森久和, 藤井敬子, 藤井伸治, 前田嘉信

日本造血・免疫細胞療法学会総会プログラム・抄録集 45th 2022

Influence of oral microbiota on graft-versus-host disease and its role as a therapeutic target

神原由依, 藤原英晃, 山本晃, 國廣まり, 大山矩史, 近藤匠, 淺田騰, 遠西大輔, 西森久和, 藤井伸治, 藤井敬子, 松岡賢市, 前田嘉信, 前田嘉信

日本造血・免疫細胞療法学会総会プログラム・抄録集 45th 2022

Gilteritinib maintenance therapy post-SCT improves the prognosis of patients with R/R FLT3mut AML

寺尾俊紀, 松岡賢市, 植田裕子, 松村彰文, 松原千哲, 近藤歌穂, 近藤匠, 藤原英晃, 淺田騰, 遠西大輔, 西森久和, 藤井敬子, 藤井伸治, 前田嘉信

日本造血・免疫細胞療法学会総会プログラム・抄録集 45th 2022

Open-label, randomized study to calcium drink for prevention of citrate toxicity of PBSC donor

藤井敬子, 藤井敬子, 藤井伸治, 藤井伸治, 三橋利晴, 住居優一, 住居優一, 谷勝真, 谷勝真, 浦田知宏, 浦田知宏, 木村真衣子, 木村真衣子, 近藤匠, 藤原英晃, 淺田騰, 遠西大輔, 西森久和, 松岡賢市, 大塚文男, 前田嘉信

日本造血・免疫細胞療法学会総会プログラム・抄録集 45th 2022

Prognostic impact of Day 30 WT1 after PTCY-haplo in myeloid neoplasm: A multi-center study from OHSG

北村亘, 藤井伸治, 藤井伸治, 名和由一郎, 杉浦弘幸, 藤下惠悟, 吉岡尚徳, 藤原悠紀, 大山矩史, 村上裕之, 高須賀裕樹, 池内一廣, 池川俊太郎, 池川俊太郎, 藤原英晃, 淺田騰, 遠西大輔, 遠西大輔, 西森久和, 藤井敬子, 松岡賢市, 木口亨, 今井利, 平松靖史, 前田嘉信

日本血液学会学術集会抄録(Web) 83rd 2021

EBV viremia with NK/T cells as well as B cells after hematopoietic stem cell transplantation

大山矩史, 西森久和, 村上裕之, 高須賀裕樹, 北村亘, 藤原英晃, 淺田騰, 藤井敬子, 藤井伸治, 遠西大輔, 松岡賢市, 前田嘉信

日本血液学会学術集会抄録(Web) 83rd 2021

移植後シクロホスファミドを用いた血縁者間HLA半合致移植後に最重症遅発性肝類洞閉塞症候群を合併した非定型慢性骨髄性白血病

北村亘, 藤井伸治, 藤井伸治, 大西秀樹, 高須賀裕樹, 大山矩史, 村上裕之, 木村真衣子, 近藤匠, 松田真幸, 池川俊太郎, 池川俊太郎, 藤原英晃, 淺田騰, 遠西大輔, 遠西大輔, 西森久和, 藤井敬子, 藤井敬子, 松岡賢市, 木口亨, 柳井広之, 吉野正, 前田嘉信

臨床血液 62 ( 6 ) 654 - 655 2021

Marfan症候群に先天性第XI因子欠乏症とvon Willebrand病(VWD)を合併した患者の心臓弁膜症手術の周術期管理

大山矩史, 淺田騰, 末澤孝徳, 新谷憲治, 廣田真規, 池内一廣, 北村亘, 高須賀裕樹, 藤原英晃, 遠西大輔, 西森久和, 藤井伸治, 松岡賢市, 笠原真悟, 前田嘉信

臨床血液 62 ( 6 ) 663 - 663 2021

Efficacy of HLA virtual cross-matched platelet transfusions for platelet transfusion refractoriness in hematopoietic stem cell transplantation (vol 60, pg 473, 2020)

Keisuke Seike, Nobuharu Fujii, Naomi Asano, Shigenori Ohkuma, Yasushi Hirata, Keiko Fujii, Yasuhisa Sando, Makoto Nakamura, Kazunori Naito, Yusuke Meguri, Noboru Asada, Daisuke Ennishi, Hisakazu Nishimori, Ken-ichi Matsuoka, Kazuo Tsubaki, Fumio Otsuka, Yoshinobu Maeda

TRANSFUSION 60 ( 11 ) 2765 - 2765 2020.11

同種骨髄移植が有用であった大脳型に進展した副腎白質ジストロフィーの1例

表芳夫, 佐藤恒太, 浦田知宏, 藤井伸治, 下澤伸行, 山下徹, 武本麻美, 菱川望, 太田康之, 阿部康二

臨床神経学 60 ( Suppl. ) S416 - S416 2020.11

原発性マクログロブリン血症から形質転換したGerminal Center B-cellタイプのびまん性大細胞型B細胞リンパ腫の症例

小林宏紀, 淺田騰, 遠西大輔, 阿部将也, 池田知佳, 坂本美彩, 江草侑厘安, 廻勇輔, 西森久和, 藤井伸治, 松岡賢市, 佐藤康晴, 吉野正, 前田嘉信

日本リンパ網内系学会会誌 60 82 - 82 2020.7

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MISC - FUJII Nobuharu