Details of the Researcher

PHOTO

Hiroki Kato
Section
Tohoku University Hospital
Job title
Senior Assistant Professor
Degree

  • PhD (Tohoku University)

Research Areas 1

  • Life sciences / Hematology and oncology /

Papers 33

  1. Shifting IRES versus Cap-initiated translation during homeostatic stem cell differentiation and stress. International-journal

    Michael C Mazzola, Ting Zhao, Anna Kiem, Trine A Kristiansen, Karin Gustafsson, Lai Ping Wong, Emily Scott-Solomon, Marissa D Fahlberg, Christina Mayerhofer, Ernst Mayerhofer, Sarah Forward, Emane Rose Assita, Giulia Schiroli, Maris Handley, Youmna Kfoury, Tsuyoshi Fukushima, Dan Li, Samuel Keyes, Azeem Sharda, Jelena Milosevic, Hiroki Kato, Pavel Ivanov, David B Sykes, Sheldon J J Kwok, Ruslan I Sadreyev, Vijay G Sankaran, Ya-Chieh Hsu, David T Scadden

    Science advances　12　(21)　eadz7896　2026/05/22

    DOI： 10.1126/sciadv.adz7896 　

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    Cell stress can increase the use of methylated guanosine (m7G) cap-independent, internal ribosome entry site (IRES)-mediated translation initiation relative to cap-dependent translation (IRES/Cap). Reporters that quantify IRES/Cap have demonstrated differential activity across cultured cell types and stress conditions. By generating an IRES/Cap reporter mouse, we were able to systematically evaluate IRES/Cap across distinct tissues and cell types during physiological stresses and lineage commitment. Caloric stress invoked the expected boost in IRES/Cap translation regardless of differentiation state, but unexpectedly, IRES/Cap progressively increased during hematopoietic and epithelial (hair follicle) differentiation under normal, homeostatic conditions. This was independent of total protein output or cell cycle. Even within cells of a given differentiation state, cells with lower relative IRES utilization had markedly higher multipotent capability in vivo. The RNA processing protein PTBP1 is a mediator of this translation initiation preference. Therefore, low IRES/Cap is a signature of high stemness and suggests that modulation of translation initiation participates in cell differentiation state.

  2. Heme synthesis inhibition induces the intrinsic apoptosis pathway in leukemia with OSGIN1 upregulation. International-journal

    Yan Yan, Hiroki Kato, Sayaka Sano, Eijiro Furukawa, Satoshi Ichikawa, Koichi Onodera, Yasushi Onishi, Noriko Fukuhara, Hisayuki Yokoyama, Tohru Fujiwara, Hideo Harigae

    Experimental hematology　157　105401-105401　2026/05

    DOI： 10.1016/j.exphem.2026.105401 　

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    Acute myeloid leukemia (AML) is one of the hematologic malignancies with a poor outcome. AML has a unique metabolic status, and identifying its metabolic vulnerabilities is warranted. Recent genome-wide screenings suggest that heme synthesis might be such a vulnerability. Heme is required not only for hemoglobin synthesis but also for the proper function of hemoproteins. Cytochromes are such hemoproteins and are necessary for mitochondrial respiration. Therefore, heme synthesis inhibition can diminish AML by altering mitochondrial status and function. However, still little is known about the importance of heme synthesis in leukemia cells. To reveal the roles of heme synthesis in leukemia, we treated human leukemia cell lines with heme synthesis inhibitors, succinylacetone (SA) or N-methyl protoporphyrin IX (NMPP). Heme synthesis inhibition induced cell growth inhibition and cell death in a concentration-dependent manner. Therefore, heme synthesis is required for leukemia cell proliferation and survival. Increased proapoptotic factors (cleaved caspase 3 and cleaved PARP) and decreased antiapoptotic factor (XIAP) were observed following heme synthesis inhibition. Cytochrome c and Smac were released into the cytoplasm by heme synthesis inhibition, suggesting that heme synthesis inhibition led to mitochondrial outer membrane permeabilization and activation of the intrinsic pathway of apoptosis. Comprehensive transcriptomic analysis revealed that heme synthesis inhibition induced OSGIN1 expression, leading to the release of cytochrome c and Smac from mitochondria into the cytoplasm. Therefore, heme synthesis inhibition induced leukemia apoptosis by activating the intrinsic apoptosis pathway.

  3. 転写因子GATA2による多能性前駆細胞におけるミエロイド系-リンフォイド系分化の運命制御

    田中 悠也, 加藤 浩貴, 佐野 さやか, 道又 大吾, 櫻井 一貴, 橋本 和貴, 諸田 直哉, 郷野 辰幸, 石井 悠翔, 小野寺 晃一, 八田 俊介, 大西 康, 藤原 亨, 福原 規子, 張替 秀郎

    日本血液学会学術集会　87回　O2-6　2025/10

    Publisher: (一社)日本血液学会

  4. High FCGR2B Expression Can Identify Low-tumor-burden Follicular Lymphoma Patients Who Do Not Require Any Antilymphoma Therapy for a Long Term. International-journal

    Shotaro Watanabe, Hiroki Kato, Tohru Fujiwara, Shunsuke Hatta, Yasuo Tomiya, Koichi Onodera, Satoshi Ichikawa, Yasushi Onishi, Hisayuki Yokoyama, Fumiyoshi Fujishima, Ryo Ichinohasama, Hideo Harigae, Noriko Fukuhara

    The American journal of surgical pathology　49　(7)　740-747　2025/07/01

    DOI： 10.1097/PAS.0000000000002397 　

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    Spontaneous regression or a long-term lack of obvious progression is often observed in patients with low-tumor-burden (LTB) follicular lymphoma (FL). However, conventional prognostic risk models are unable to precisely identify the patients who will not require any antilymphoma treatment for a long term, especially at diagnosis. In this study, we identified genes whose expression levels were associated with the clinical outcome of LTB FL and verified their prognostic value using immunohistochemistry. Because the tumor microenvironment may influence FL pathogenesis, we used digital expression profiling to quantify the expression of 730 immune-related genes extracted from tumor tissue specimens collected from 55 untreated patients with LTB FL. Five genes were identified as potential transcriptomic predictive markers. Among these, FCGR2B , an inhibitory FC gamma receptor, was immunohistochemically stainable and identified as a reliable immunohistochemical prognostic marker mainly expressed in tumor cells but not in the surrounding reactive cells. Our findings could help identify patients with LTB FL who do not require any antilymphoma treatment for the long term.

  5. Angioimmunoblastic T-cell lymphoma harboring a t(8;14)(q24;q11.2)/TCR::MYC translocation that presented with intestinal infiltration. International-journal

    Satoshi Ichikawa, Hiroki Kato, Naoya Morota, Hiroaki Abe, Akihisa Kawajiri, Kyoko Inokura, Koichi Onodera, Yasushi Onishi, Noriko Fukuhara, Satoko Sato, Fumiyoshi Fujishima, Ryo Ichinohasama, Hideo Harigae

    Annals of hematology　2024/12/18

    DOI： 10.1007/s00277-024-06148-2 　

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    Although rearrangement of the MYC oncogene (MYC-R) is frequently observed in aggressive B-cell lymphomas, it is extremely rare in T-cell malignancies. A 64-year-old man who had been under observation for several years because of asymptomatic pulmonary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALToma) was admitted to our hospital because of poor general condition and hypotension. Blood tests revealed thrombocytopenia and elevated serum lactate dehydrogenase levels, whereas computed tomography revealed systemic lymphadenopathy and splenomegaly. An inguinal lymph node biopsy precipitated a diagnosis of angioimmunoblastic T-cell lymphoma (AITL). Shortly after admission, the patient experienced spontaneous intestinal perforation and hemorrhage caused by multiple intestinal infiltrations of the AITL. Although chemotherapy was administered, the patient died several weeks after admission. A 46,XY,t(8;14)(q24;q11.2) karyotype was identified, and fluorescence in situ hybridization analyses showed split signals for the MYC and T-cell receptor (TCR) alpha genes, by which a TCR::MYC translocation was confirmed. Pathological autopsy analysis revealed systemic infiltration of the AITL and no MALToma lesions. Only a few cases of mature T-cell lymphoma harboring MYC-R have been reported in the literature thus far. To the best of our knowledge, this is the first reported case of AITL with TCR::MYC rearrangement. This condition could be associated with refractoriness to chemotherapy and aggressive clinical course with systemic infiltration that included the intestine.

  6. T細胞とミエロイド細胞の運命決定におけるGata2の役割

    佐野 沙矢香, 加藤 浩貴, 古川 瑛次郎, 燕 艶, 道又 大吾, 田中 悠也, 櫻井 一貴, 小野寺 晃一, 市川 聡, 福原 規子, 大西 康, 横山 寿行, 藤原 亨, 張替 秀郎

    日本血液学会学術集会　86回　O1-1　2024/10

    Publisher: (一社)日本血液学会

  7. 造血幹前駆細胞におけるSAM合成によるDNAの安定化とp53経路抑制を介した恒常性の維持

    古川 瑛次郎, 加藤 浩貴, 佐野 沙矢香, 燕 艶, 道又 大吾, 田中 裕也, 櫻井 一貴, 小野寺 晃一, 市川 聡, 福原 規子, 大西 康, 横山 寿行, 三枝 大輔, 藤原 亨, 五十嵐 和彦, 張替 秀郎

    日本血液学会学術集会　86回　O1-4　2024/10

    Publisher: (一社)日本血液学会

  8. t(8;14)(q24;q11.2)/TCR::MYCを伴った血管免疫芽球性T細胞リンパ腫

    市川 聡, 加藤 浩貴, 諸田 直哉, 安部 宇明, 川尻 昭寿, 猪倉 恭子, 中川 諒, 八田 俊介, 小野寺 晃一, 福原 規子, 大西 康, 横山 寿行, 藤島 史喜, 一迫 玲, 張替 秀郎

    日本血液学会学術集会　86回　P2-6　2024/10

    Publisher: (一社)日本血液学会

  9. T細胞とミエロイド細胞の運命決定におけるGata2の役割

    佐野 沙矢香, 加藤 浩貴, 古川 瑛次郎, 燕 艶, 道又 大吾, 田中 悠也, 櫻井 一貴, 小野寺 晃一, 市川 聡, 福原 規子, 大西 康, 横山 寿行, 藤原 亨, 張替 秀郎

    日本血液学会学術集会　86回　O1-1　2024/10

    Publisher: (一社)日本血液学会

  10. 造血幹前駆細胞におけるSAM合成によるDNAの安定化とp53経路抑制を介した恒常性の維持

    古川 瑛次郎, 加藤 浩貴, 佐野 沙矢香, 燕 艶, 道又 大吾, 田中 裕也, 櫻井 一貴, 小野寺 晃一, 市川 聡, 福原 規子, 大西 康, 横山 寿行, 三枝 大輔, 藤原 亨, 五十嵐 和彦, 張替 秀郎

    日本血液学会学術集会　86回　O1-4　2024/10

    Publisher: (一社)日本血液学会

  11. t(8;14)(q24;q11.2)/TCR::MYCを伴った血管免疫芽球性T細胞リンパ腫

    市川 聡, 加藤 浩貴, 諸田 直哉, 安部 宇明, 川尻 昭寿, 猪倉 恭子, 中川 諒, 八田 俊介, 小野寺 晃一, 福原 規子, 大西 康, 横山 寿行, 藤島 史喜, 一迫 玲, 張替 秀郎

    日本血液学会学術集会　86回　P2-6　2024/10

    Publisher: (一社)日本血液学会

  12. フローサイトメトリー検査実践講座2023 MALTリンパ腫の経過中にT細胞リンパ腫を発症し診断に苦慮した1症例

    大久保 礼由, 菅原 新吾, 鈴木 千恵, 武田 卓也, 安 久美子, 石塚 静江, 真山 晃史, 牧 優治, 吉岡 翔, 阿部 裕子, 藤巻 慎一, 加藤 浩貴, 市川 聡, 福原 規子, 亀井 尚

    日本臨床検査医学会誌　72　(9)　761-767　2024/09

    Publisher: (一社)日本臨床検査医学会

    ISSN： 2436-2727

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    症例は60歳代男性で、MALTリンパ腫(節外性濾胞辺縁帯粘膜関連リンパ組織型リンパ腫)の経過観察中の末梢血液像、骨髄像で異常細胞を認めた。MALTリンパ腫を念頭に骨髄のフローサイトメトリー(FCM)を実施したが、明らかな異常所見は認めず、T細胞リンパ腫の可能性が考えて追加検査を行った。その結果、骨髄染色体G分染法では46,XY,t(8;14)(q24;q11.2)が検出され、鼠径リンパ節の病理組織診断は血管免疫芽球性T細胞リンパ腫であった。FCMの再解析にて異常細胞の集団ではCD4 +CD8が74.0%、CD3が50.4%と乖離がみられ、健常人より多く存在したCD7(-)、CD2(+)の細胞集団はsCD3(-)、CD4(+)、CD8(-)、CD5(+)の異常T細胞と推察された。T細胞リンパ腫由来の異常細胞を検出する際、T細胞抗原のバランスを確認することが有効であった。

  13. フローサイトメトリー検査実践講座2023 MALTリンパ腫の経過中にT細胞リンパ腫を発症し診断に苦慮した1症例

    大久保 礼由, 菅原 新吾, 鈴木 千恵, 武田 卓也, 安 久美子, 石塚 静江, 真山 晃史, 牧 優治, 吉岡 翔, 阿部 裕子, 藤巻 慎一, 加藤 浩貴, 市川 聡, 福原 規子, 亀井 尚

    日本臨床検査医学会誌　71　(補冊)　054-054　2023/10

    Publisher: (一社)日本臨床検査医学会

    ISSN： 2436-2727

  14. 正常造血及び白血病におけるヘム合成の役割

    燕 艶, 加藤 浩貴, 佐野 沙矢香, 古川 瑛次郎, 藤原 亨, 大西 康, 福原 規子, 横山 寿行, 張替 秀郎

    日本血液学会学術集会　85回　934-934　2023/10

    Publisher: (一社)日本血液学会

  15. Limited plasticity of monocyte fate and function associated with epigenetic scripting at the level of progenitors. International-journal

    Catherine Rhee, Elizabeth W Scadden, Lai Ping Wong, Giulia Schiroli, Michael C Mazzola, Phillip L Chea, Hiroki Kato, Friedrich F Hoyer, Meeta Mistry, Bum-Kyu Lee, Jonghwan Kim, Matthias Nahrendorf, Michael K Mansour, David B Sykes, Ruslan I Sadreyev, David T Scadden

    Blood　142　(7)　658-674　2023/08/17

    DOI： 10.1182/blood.2023020257 　

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    Myeloid cell heterogeneity is known, but whether it is cell-intrinsic or environmentally-directed remains unclear. Here, an inducible/reversible system pausing myeloid differentiation allowed the definition of clone-specific functions that clustered monocytes into subsets with distinctive molecular features. These subsets were orthogonal to the classical/nonclassical categorization and had inherent, restricted characteristics that did not shift under homeostasis, after irradiation, or with infectious stress. Rather, their functional fate was constrained by chromatin accessibility established at or before the granulocyte-monocyte or monocyte-dendritic progenitor level. Subsets of primary monocytes had differential ability to control distinct infectious agents in vivo. Therefore, monocytes are a heterogeneous population of functionally restricted subtypes defined by the epigenome of their progenitors that are differentially selected by physiologic challenges with limited plasticity to transition from one subset to another.

  16. [Gene regulatory networks operated by iron-heme metabolism: focusing on the erythroid differentiation system].

    Kato H, Igarashi K

    [Rinsho ketsueki] The Japanese journal of clinical hematology　2023/01/01

    DOI： 10.11406/rinketsu.64.406 　

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    Recently, attention has been focused on how metabolites regulate cellular differentiation. Heme synthesis is greatly enhanced during erythroid differentiation. Heme is used for hemoglobin synthesis, which is needed for oxygen transport by red blood cells. Additionally, several pieces of evidence revealed that heme may control gene expression to fulfill erythroblast terminal maturation. For instance, heme binds to and inactivates the transcription factor BTB Domain And CNC Homolog 1 (BACH1), thereby inducing the globin gene expression, which is the repressive target of BACH1. Moreover, heme induces autophagy/mitophagy-related gene expressions, which are the targets of the transcription factor GATA1 and may promote erythrocyte maturation by itself. Heme may directly bind to guanine tetramer (G-quadruplex) regions of genomic DNA, thereby regulating nearby gene expressions. Here, we present an overview of the mechanism by which iron-heme metabolism regulates gene regulatory networks by focusing on the erythroid differentiation system. Additionally, we discuss the prospects of future research regarding iron-heme metabolism.

  17. Elucidation of the Role of FAM210B in Mitochondrial Metabolism and Erythropoiesis. International-journal

    Chie Suzuki, Tohru Fujiwara, Hiroki Shima, Koya Ono, Kei Saito, Hiroki Kato, Koichi Onodera, Satoshi Ichikawa, Noriko Fukuhara, Yasushi Onishi, Hisayuki Yokoyama, Yukio Nakamura, Kazuhiko Igarashi, Hideo Harigae

    Molecular and cellular biology　42　(12)　e0014322　2022/12/15

    DOI： 10.1128/mcb.00143-22 　

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    Mitochondria play essential and specific roles during erythroid differentiation. Recently, FAM210B, encoding a mitochondrial inner membrane protein, has been identified as a novel target of GATA-1, as well as an erythropoietin-inducible gene. While FAM210B protein is involved in regulate mitochondrial metabolism and heme biosynthesis, its detailed function remains unknown. Here, we generated both knockout and knockdown of endogenous FAM210B in human induced pluripotent stem-derived erythroid progenitor (HiDEP) cells using CRISPR/Cas9 methodology. Intriguingly, erythroid differentiation was more pronounced in the FAM210B-depleted cells, and this resulted in increased frequency of orthochromatic erythroblasts and decreased frequencies of basophilic/polychromatic erythroblasts. Comprehensive metabolite analysis and functional analysis indicated that oxygen consumption rates and the NAD (NAD+)/NADH ratio were significantly decreased, while lactate production was significantly increased in FAM210B deletion HiDEP cells, indicating involvement of FAM210B in mitochondrial energy metabolism in erythroblasts. Finally, we purified FAM210B-interacting protein from K562 cells that stably expressed His/biotin-tagged FAM210B. Mass spectrometry analysis of the His/biotin-purified material indicated interactions with multiple subunits of mitochondrial ATP synthases, such as subunit alpha (ATP5A) and beta (ATP5B). Our results suggested that FAM210B contributes prominently to erythroid differentiation by regulating mitochondrial energy metabolism. Our results provide insights into the pathophysiology of dysregulated hematopoiesis.

  18. Heme-dependent induction of mitophagy program during differentiation of murine erythroid cells. International-journal

    Masatoshi Ikeda, Hiroki Kato, Hiroki Shima, Mitsuyo Matsumoto, Eijiro Furukawa, Yan Yan, Ruiqi Liao, Jian Xu, Akihiko Muto, Tohru Fujiwara, Hideo Harigae, Emery H Bresnick, Kazuhiko Igarashi

    Experimental hematology　118　21-30　2022/12/05

    DOI： 10.1016/j.exphem.2022.11.007 　

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    Although establishment and maintenance of mitochondria are essential for the production of massive amounts of heme in erythroblasts, mitochondria must be degraded upon terminal differentiation to red blood cells (RBCs), thus creating a biphasic regulatory process. Previously, we reported that iron deficiency in mice promotes mitochondrial retention in RBCs, suggesting that a proper amount of iron and/or heme is necessary for the degradation of mitochondria during erythroblast maturation. Because the transcription factor GATA1 regulates autophagy in erythroid cells, which involves mitochondrial clearance (mitophagy), we investigated the relationship between iron or heme and mitophagy by analyzing the expression of genes related to GATA1 and autophagy and the impact of iron or heme restriction on the amount of mitochondria. We found that heme promotes the expression of GATA1-regulated mitophagy-related genes and the induction of mitophagy. GATA1 might induce the expression of the autophagy-related genes Atg4d and Stk11 for mitophagy through a heme-dependent mechanism in murine erythroleukemia (MEL) cells and a genetic rescue system with G1E-ER-GATA1 erythroblast cells derived from Gata1-null murine embryonic stem cells. These results provide evidence for a biphasic mechanism in which mitochondria are essential for heme generation, and the heme generated during differentiation promotes mitophagy and mitochondrial disposal. This mechanism provides a molecular framework for understanding this fundamentally important cell biological process.

  19. Exploring the mechanistic link between SF3B1 mutation and ring sideroblast formation in myelodysplastic syndrome. International-journal

    Tetsuro Ochi, Tohru Fujiwara, Koya Ono, Chie Suzuki, Maika Nikaido, Daichi Inoue, Hiroki Kato, Koichi Onodera, Satoshi Ichikawa, Noriko Fukuhara, Yasushi Onishi, Hisayuki Yokoyama, Yukio Nakamura, Hideo Harigae

    Scientific reports　12　(1)　14562-14562　2022/08/26

    DOI： 10.1038/s41598-022-18921-2 　

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    Acquired sideroblastic anemia, characterized by bone marrow ring sideroblasts (RS), is predominantly associated with myelodysplastic syndrome (MDS). Although somatic mutations in splicing factor 3b subunit 1 (SF3B1), which is involved in the RNA splicing machinery, are frequently found in MDS-RS, the detailed mechanism contributing to RS formation is unknown. To explore the mechanism, we established human umbilical cord blood-derived erythroid progenitor-2 (HUDEP-2) cells stably expressing SF3B1K700E. SF3B1K700E expressing cells showed higher proportion of RS than the control cells along with erythroid differentiation, indicating the direct contribution of mutant SF3B1 expression in erythroblasts to RS formation. In SF3B1K700E expressing cells, ABCB7 and ALAS2, known causative genes for congenital sideroblastic anemia, were downregulated. Additionally, mis-splicing of ABCB7 was observed in SF3B1K700E expressing cells. ABCB7-knockdown HUDEP-2 cells revealed an increased frequency of RS formation along with erythroid differentiation, demonstrating the direct molecular link between ABCB7 defects and RS formation. ALAS2 protein levels were obviously decreased in ABCB7-knockdown cells, indicating decreased ALAS2 translation owing to impaired Fe-S cluster export by ABCB7 defects. Finally, RNA-seq analysis of MDS clinical samples demonstrated decreased expression of ABCB7 by the SF3B1 mutation. Our findings contribute to the elucidation of the complex mechanisms of RS formation in MDS-RS.

  20. Congenital sideroblastic anemia model due to ALAS2 mutation is susceptible to ferroptosis. International-journal

    Koya Ono, Tohru Fujiwara, Kei Saito, Hironari Nishizawa, Noriyuki Takahashi, Chie Suzuki, Tetsuro Ochi, Hiroki Kato, Yusho Ishii, Koichi Onodera, Satoshi Ichikawa, Noriko Fukuhara, Yasushi Onishi, Hisayuki Yokoyama, Rie Yamada, Yukio Nakamura, Kazuhiko Igarashi, Hideo Harigae

    Scientific reports　12　(1)　9024-9024　2022/05/30

    DOI： 10.1038/s41598-022-12940-9 　

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    X-linked sideroblastic anemia (XLSA), the most common form of congenital sideroblastic anemia, is caused by a germline mutation in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene. In XLSA, defective heme biosynthesis leads to ring sideroblast formation because of excess mitochondrial iron accumulation. In this study, we introduced ALAS2 missense mutations on human umbilical cord blood-derived erythroblasts; hereafter, we refer to them as XLSA clones. XLSA clones that differentiated into mature erythroblasts showed an increased frequency of ring sideroblast formation with impaired hemoglobin biosynthesis. The expression profiling revealed significant enrichment of genes involved in ferroptosis, which is a form of regulated cell death induced by iron accumulation and lipid peroxidation. Notably, treatment with erastin, a ferroptosis inducer, caused a higher proportion of cell death in XLSA clones. XLSA clones exhibited significantly higher levels of intracellular lipid peroxides and enhanced expression of BACH1, a regulator of iron metabolism and potential accelerator of ferroptosis. In XLSA clones, BACH1 repressed genes involved in iron metabolism and glutathione synthesis. Collectively, defective heme biosynthesis in XLSA clones could confer enhanced BACH1 expression, leading to increased susceptibility to ferroptosis. The results of our study provide important information for the development of novel therapeutic targets for XLSA.

  21. TM5614, an Inhibitor of Plasminogen Activator Inhibitor-1, Exerts an Antitumor Effect on Chronic Myeloid Leukemia.

    Katsuyuki Sasaki, Tohru Fujiwara, Tetsuro Ochi, Koya Ono, Hiroki Kato, Koichi Onodera, Satoshi Ichikawa, Noriko Fukuhara, Yasushi Onishi, Hisayuki Yokoyama, Toshio Miyata, Hideo Harigae

    The Tohoku journal of experimental medicine　2022/04/28

    DOI： 10.1620/tjem.2022.J036 　

  22. Unrelated cord blood transplantation for adult-onset EBV-associated T-cell and NK-cell lymphoproliferative disorders.

    Yasushi Onishi, Koichi Onodera, Noriko Fukuhara, Hiroki Kato, Satoshi Ichikawa, Tohru Fujiwara, Hisayuki Yokoyama, Minami Yamada-Fujiwara, Hideo Harigae

    International journal of hematology　115　(6)　873-881　2022/03/10

    DOI： 10.1007/s12185-022-03313-z 　

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    Adult-onset EBV-associated T-cell and NK-cell lymphoproliferative disorders (EBV-T/NK-LPDs) often progress rapidly, and require allogeneic stem cell transplantation early in the course of treatment. Unrelated cord blood transplantation (UCBT) is a readily available option for patients without HLA-matched donors. We retrospectively analyzed the outcomes of 12 UCBT in adult patients with chronic active EBV infection (CAEBV, n = 8), EBV-positive hemophagocytic lymphohistiocytosis following primary EBV infection (n = 2), hydroa vacciniforme-like lymphoproliferative disorder (n = 1), and systemic EBV-positive T-cell lymphoma of childhood (STCLC, n = 1). The median age at transplantation was 31.5 years (range 19-58). At the median follow-up time for survivors, which was 6.3 years (range 0.3-11.3), 3-year overall survival (OS) rates in all patients and 8 CAEBV patients were 68.2% (95% CI 28.6-88.9) and 83.3% (95% CI 27.3-97.5), respectively. Graft failure occurred in 4 of 8 CAEBV patients, requiring a second UCBT to achieve neutrophil engraftment. The cumulative incidence of grade II-IV acute GVHD was 33.3% (95% CI 9.1-60.4%). The EBV-DNA load became undetectable or very low after UCBT in all cases. UCBT may be a promising treatment option for adult-onset EBV-T/NK-LPDs.

  23. Low NCOR2 levels in multiple myeloma patients drive multidrug resistance via MYC upregulation. International-journal

    Tomoaki Mori, Rakesh Verma, Rie Nakamoto-Matsubara, Ka Tat Siu, Cristina Panaroni, Keertik S Fulzele, Kenta Mukaihara, Chukwuamaka Onyewadume, Allison Maebius, Hiroki Kato, Lai Ping Wong, Ruslan I Sadreyev, David T Scadden, Noopur S Raje

    Blood cancer journal　11　(12)　194-194　2021/12/04

    DOI： 10.1038/s41408-021-00589-y 　

    More details Close

    MYC upregulation is associated with multidrug refractory disease in patients with multiple myeloma (MM). We, isolated patient-derived MM cells with high MYC expression and discovered that NCOR2 was down-regulated in these cells. NCOR2 is a transcriptional coregulatory protein and its role in MM remains unknown. To define the role of NCOR2 in MM, we created NCOR2 knockout human myeloma cell lines and demonstrated that NCOR2 knockout led to high MYC expression. Furthermore, NCOR2 knockout conferred resistance to pomalidomide, BET and HDAC inhibitors, independent of Cereblon (CRBN), indicating high MYC expression as a cause of multidrug resistance. Moreover, NCOR2 interacted with the nucleosome remodeling and deacetylase (NuRD) complex and repressed the expression of CD180 by directly binding to its promoter and inducing MYC expression. Next, we generated lenalidomide-resistant and pomalidomide-resistant human myeloma cell lines. Whole-exome sequencing revealed that these cell lines acquired the same exonic mutations of NCOR2. These cell lines showed NCOR2 downregulation and MYC upregulation independent of CRBN and demonstrated resistance to BET and HDAC inhibitors. Our findings reveal a novel CRBN independent molecular mechanism associated with drug resistance. Low NCOR2 expression can serve as a potential biomarker for drug resistance and needs further validation in larger prospective studies.

  24. 幹細胞から赤血球への通り道 メチオニン代謝によるエピゲノム調節をかいした赤血球造血制御(Methionine metabolism controls erythropoiesis by epigenetic regulation)

    加藤 浩貴, Long Nugyen, 石井 悠翔, 松本 光代, 三枝 大輔, 舟山 亮, 岡江 寛明, 藤原 亨, 武藤 哲彦, 中山 啓子, 有馬 隆博, Scadden David, 五十嵐 和彦, 張替 秀郎

    日本血液学会学術集会　83回　PSY-4　2021/09

    Publisher: (一社)日本血液学会

  25. 遺伝情報を調節するメチル化連動システム S-アデノシルメチオニン代謝系による遺伝子発現の調節機構

    五十嵐 和彦, Nguyen Long Chi, 石井 悠翔, 加藤 浩貴, 落合 恭子, 松本 光代, 島 弘季

    日本生化学会大会プログラム・講演要旨集　93回　[3S02m-03]　2020/09

    Publisher: (公社)日本生化学会

  26. 環境変化に応じた造血系の恒常性維持におけるBach因子群の役割

    加藤 浩貴, 五十嵐 和彦

    臨床免疫・アレルギー科　72　(5)　535-540　2019/11

    Publisher: (有)科学評論社

    ISSN： 1881-1930

  27. 細胞内SAM濃度レポーターに基づいたスクリーニング系による新規MAT2A阻害剤の同定

    奈良 和樹, 石井 悠翔, 加藤 浩貴, 島 弘季, 五十嵐 和彦

    日本生化学会大会プログラム・講演要旨集　92回　[2T13m-06]　2019/09

    Publisher: (公社)日本生化学会

  28. 血液内科学 Bach因子群と赤血球造血

    加藤 浩貴, 五十嵐 和彦

    医学のあゆみ　270　(11)　1079-1080　2019/09

    Publisher: 医歯薬出版(株)

    ISSN： 0039-2359

  29. 細胞内SAM濃度レポーターに基づいたスクリーニング系による新規MAT2A阻害剤の同定

    奈良 和樹, 石井 悠翔, 加藤 浩貴, 島 弘季, 五十嵐 和彦

    日本生化学会大会プログラム・講演要旨集　92回　[2T13m-06]　2019/09

    Publisher: (公社)日本生化学会

  30. 転写因子ネットワークによる血液細胞分化の調節とその病態

    加藤 浩貴, 五十嵐 和彦

    臨床血液　59　(10)　1872-1879　2018/10

    Publisher: (一社)日本血液学会-東京事務局

    ISSN： 0485-1439

    eISSN： 1882-0824

  31. 転写因子Bach1及びBach2の環境変化に応じた赤血球-ミエロイド分化制御(Bach1 and Bach2 orchestrate erythro-myeloid differentiation responding to environmental changes)

    Kato Hiroki, Itoh Ari, Matsumoto Mitsuyo, Shibuya Risa, Sato Yuki, Kobayashi Masahiro, Muto Akihiko, Fujiwara Tohru, Harigae Hideo, Igarashi Kazuhiko

    臨床血液　58　(9)　1489-1489　2017/09

    Publisher: (一社)日本血液学会-東京事務局

    ISSN： 0485-1439

    eISSN： 1882-0824

  32. 細胞外環境を転写とエピゲノムへ統合する分子機構 Inner Myeloidの遺伝子制御ネットワークとその環境応答機構

    五十嵐 和彦, 加藤 浩貴, 張替 秀郎, 武藤 哲彦, 松本 光代, 伊藤 亜里, AMED-CREST

    日本生化学会大会プログラム・講演要旨集　89回　[2S01-2]　2016/09

    Publisher: (公社)日本生化学会

  33. 鉄生化学の新しい潮流 ヘム-Bach1経路は鉄欠乏下での適応的な赤血球新生を調節する(The heme-Bach1 pathway regulates the adaptive erythropoiesis under iron deficiency)

    五十嵐 和彦, 小林 匡洋, 加藤 浩貴, 伊藤 亜里

    日本生化学会大会プログラム・講演要旨集　87回　[2S12a-1]　2014/10

    Publisher: (公社)日本生化学会

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Misc. 7

  1. ヒト赤芽球細胞株を用いた造血性プロトポルフィリン症の病態解明

    二階堂舞香, 藤原亨, 鈴木千恵, 鈴木千恵, 小野浩弥, 加藤浩貴, 小野寺晃一, 市川聡, 福原規子, 大西康, 横山寿行, 中村幸夫, 張替秀郎, 張替秀郎

    日本鉄バイオサイエンス学会学術集会プログラム・抄録集　47th　2023

  2. Methionine metabolism controls erythropoiesis by epigenetic regulation

    加藤浩貴, 加藤浩貴, 加藤浩貴, NGUYEN Long, 石井悠翔, 石井悠翔, 松本光代, 三枝大輔, 舟山亮, 岡江寛明, 藤原亨, 武藤哲彦, 中山啓子, 有馬隆博, SCADDEN David, 五十嵐和彦, 張替秀郎

    日本血液学会学術集会抄録(Web)　83rd　2021

  3. Cellular models of X-linked sideroblastic anemia based on immortalized human erythroid progenitors

    小野浩弥, 藤原亨, 藤原亨, 齋藤慧, 鈴木千恵, 高橋昇之, 加藤浩貴, 小野寺晃一, 市川聡, 福原規子, 大西康, 横山寿行, 中村幸夫, 張替秀郎, 張替秀郎

    日本血液学会学術集会抄録(Web)　83rd　2021

  4. FOG1-dependent transcriptional network involves glucose metabolic regulation of erythroid cells

    藤原亨, 藤原亨, 鈴木千恵, 鈴木千恵, 小野浩弥, 加藤浩貴, 小野寺晃一, 市川聡, 福原規子, 大西康, 横山寿行, 張替秀郎, 張替秀郎

    日本血液学会学術集会抄録(Web)　83rd　2021

  5. Elucidation of the role of FAM210B in mitochondrial metabolism in erythroblasts

    鈴木千恵, 鈴木千恵, 藤原亨, 藤原亨, 島弘季, 小野浩弥, 齋藤慧, 加藤浩貴, 小野寺晃一, 市川聡, 福原規子, 大西康, 横山寿行, 中村幸夫, 五十嵐和彦, 張替秀郎

    日本血液学会学術集会抄録(Web)　83rd　2021

  6. Transcription Factor Bach1 and Bach2 Operate Erythro-Myeloid Competitive Differentiation By Responding to Environmental Changes

    Hiroki Kato, Ari Itoh-Nakadai, Mitsuyo Matsumoto, Risa Ebina-Shibuya, Yuki Sato, Masahiro Kobayashi, Akihiko Muto, Tohru Fujiwara, Hideo Harigae, Kazuhiko Igarashi

    BLOOD　128　(22)　2016/12

    ISSN： 0006-4971

    eISSN： 1528-0020

  7. Transcription Factor Bach1 and Bach2 Control Common Myeloid Progenitor Cell Differentiation Under Infectious Stimuli

    Hiroki Kato, Ari Itoh-Nakadai, Risa Ebina-Shibuya, Masahiro Kobayashi, Mitsuyo Matsumoto, Akihiko Muto, Tohru Fujiwara, Hideo Harigae, Kazuhiko Igarashi

    BLOOD　126　(23)　2015/12

    ISSN： 0006-4971

    eISSN： 1528-0020

Show all ︎Show first 5

Research Projects 5

  1. ヘム合成に着目した免疫細胞分化制御機構の解明とその破綻に伴う疾患の克服

    張替 秀郎, 加藤 浩貴

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 基盤研究(B)

    Institution: 東北大学

    2024/04/01 - 2027/03/31

  2. 転写因子GATA2に着目した造血と肺血管内皮の連関解析

    張替 秀郎, 加藤 浩貴

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 挑戦的研究(萌芽)

    Institution: 東北大学

    2024/06/28 - 2026/03/31

  3. SアデノシルメチオニンのBリンパ球初期分化での役割の解明

    加藤 浩貴

    Offer Organization: 日本学術振興会

    System: 科学研究費助成事業

    Category: 若手研究

    Institution: 東北大学

    2024/04/01 - 2026/03/31

  4. Molecular basis of RNA modification in immune response after transplantation and cell therapy and novel biomarkers

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Scientific Research (C)

    Institution: Tohoku University

    2023/04/01 - 2026/03/31

  5. Regulation of acquired immune cell responses by S-adenosylmethionine metabolism and its subcellular localization

    Offer Organization: Japan Society for the Promotion of Science

    System: Grants-in-Aid for Scientific Research

    Category: Grant-in-Aid for Challenging Research (Exploratory)

    Institution: Tohoku University

    2023/06/30 - 2025/03/31