Research Experience 【 display / non-display 】

Research Experience 【 display / non-display 】

• 2025.07

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  Now

  Sapporo Medical University   Department of Hematology   Associate Professor

• 2022.04

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  Now

  Sapporo Medical University Hospital   Division of Laboratory Diagnosis   副部長

• 2021.02

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  Now

  Sapporo Medical University   血液内科学   講師

• 2007

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  2021.02

  Sapporo Medical University   School of Medicine   助教

Research Areas 【 display / non-display 】

Research Areas 【 display / non-display 】

• Life sciences   Hematology and oncology  

Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

• Sapporo Medical University Hospital   Division of Laboratory Diagnosis   副部長  

Research Interests 【 display / non-display 】

Research Interests 【 display / non-display 】

• シグナル伝達

• 分子標的

• リンパ球増幅

• 発現制御

• 臨床

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Papers 【 display / non-display 】

Papers 【 display / non-display 】

• Prognostic impact of TET2 mutations in patients with acute myeloid leukemia: HM-SCREEN-Japan 01 and 02 study.

  Satoshi Iyama, SungGi Chi, Masashi Idogawa, Takayuki Ikezoe, Kentaro Fukushima, Yoshikazu Utsu, Junya Kanda, Goichi Yoshimoto, Takahiro Kobayashi, Naoko Hosono, Takahiro Yamauchi, Takeshi Kondo, Yukinori Nakamura, Kensuke Kojima, Chikashi Yoshida, Akihiko Gotoh, Kazuhito Yamamoto, Junya Kuroda, Kenji Ishitsuka, Emiko Sakaida, Hiroto Horiguchi, Kohichi Takada, Hirofumi Ohnishi, Masayoshi Kobune, Yosuke Minami

  Annals of hematology   104 ( 1 ) 275 - 284  2025.01  [International journal]

  　View Summary

  Ten-eleven translocation-2 (TET2) gene mutations are observed in 12-20% of adult patients with acute myeloid leukemia (AML). The prognostic impact of TET2 mutations in patients with AML and myelodysplastic syndromes has been reported in several studies; however, their results remain controversial. Therefore, we aimed to analyze the prevalence and significance of TET2 mutations in patients with AML. Data were obtained from 331 patients with AML according to the Hematologic Malignancies-SCREEN-Japan 01 and 02 studies, which were prospective multicenter genomic profiling analyses. We found a distinct type of TET2 mutations, with a particularly detrimental prognosis in the patients. Thirty-five patients with TET2 'significant' mutations were identified (26 with frameshift mutations and nine with nonsense mutations). The proportion of patients with TET2 mutations was 31.7% (10.6% and 21.1% in the TET2 significant and non-significant mutation groups). The TET2 significant mutation group had a shorter OS than the TET2 non-significant mutation or wild-type TET2 group (median: 15.9 vs. 35.0 vs. 25.9 months). Regarding the response to chemotherapy according to TET2 status, the complete response (CR) or CR with incomplete count recovery rate was 37.1% in the TET2 significant mutation group and 46.6% in the non-significant mutation or wild-type group. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) improved patient prognosis in the TET2 non-significant mutation or wild-type TET2 group; however, allo-HSCT did not affect prognosis in the TET2 significant mutation group. This study indicates that certain TET2 mutations in patients with AML may have detrimental effects.

  DOI PubMed

• FLT3 inhibitors and hematopoietic cell transplantation prolong survival in patients with FLT3-ITD-positive AML.

  Toshihiro Matsukawa, Masahiro Onozawa, Takeshi Kondo, Minoru Kanaya, Daisuke Hidaka, Shuichi Ota, Akio Mori, Akio Shigematsu, Takuto Miyagishima, Yasutaka Kakinoki, Junichi Hashiguchi, Satoshi Yamamoto, Masayo Yamamoto, Kentaro Wakasa, Mutsumi Takahata, Toshimichi Ishihara, Yoshihito Haseyama, Akihito Fujimi, Tetsuya Igarashi, Takehiro Sarashina, Satoshi Iyama, Ryoji Kobayashi, Hajime Sakai, Katsuya Fujimoto, Junki Inamura, Yuji Kanisawa, Shinsuke Hirabayashi, Tomoyuki Endo, Daigo Hashimoto, Takanori Teshima

  Annals of hematology   103 ( 12 ) 5333 - 5340  2024.12  [International journal]

  　View Summary

  Acute myeloid leukemia (AML) is an aggressive hematological malignancy with genetic alterations. The FMS-like tyrosine kinase 3 (FLT3) gene is frequently mutated in adult de novo AML, with two types of mutations: internal tandem duplication (ITD) and point mutations in the tyrosine kinase domain. This study aimed to investigate the impact of FLT3 inhibitors and hematopoietic cell transplantation (HCT) on survival outcomes in patients with FLT3-ITD AML in a real-world setting. We retrospectively analyzed 139 patients with FLT3-ITD-positive AML between 2012 and 2021. The median age was 63 years. In the propensity score-matched cohort, FLT3 inhibitors improved overall survival (OS) compared with patients treated without FLT3 inhibitors (3-year OS: 33.7% vs. 25.8%, p = 0.021). Patients who underwent HCT had superior outcomes to those without HCT (3-year OS: 45.3% vs. 2.2%, p < 0.0001). The combination of FLT3 inhibitors and HCT resulted in the highest OS and relapse-free survival (RFS) rates (3-year OS: 62.4%; 3-year RFS: 44.4%). Disease status before transplantation did not predict the prognosis, but use of FLT3 inhibitors increased survival in patients without complete remission before HCT. These results demonstrate the clinical impact of FLT3 inhibitors on survival outcomes in patients with FLT3-ITD-positive AML, particularly when combined with HCT. FLT3 inhibitors can improve the prognosis of AML with FLT3 mutations, especially in patients who undergo HCT.

  DOI PubMed

• Intravenous Infusion of Autologous Mesenchymal Stem Cells Expanded in Auto Serum for Chronic Spinal Cord Injury Patients: A Case Series.

  Ryosuke Hirota, Masanori Sasaki, Satoshi Iyama, Kota Kurihara, Ryunosuke Fukushi, Hisashi Obara, Tsutomu Oshigiri, Tomonori Morita, Masahito Nakazaki, Takahiro Namioka, Ai Namioka, Rie Onodera, Yuko Kataoka-Sasaki, Shinichi Oka, Mitsuhiro Takemura, Ryo Ukai, Takahiro Yokoyama, Yuichi Sasaki, Tatsuro Yamashita, Masato Kobayashi, Yusuke Okuma, Reiko Kondo, Ryo Aichi, Satoko Ohmatsu, Noritaka Kawashima, Yoichi M Ito, Masayoshi Kobune, Kohichi Takada, Sumio Ishiai, Toru Ogata, Atsushi Teramoto, Toshihiko Yamashita, Jeffery D Kocsis, Osamu Honmou

  Journal of clinical medicine   13 ( 20 )  2024.10  [International journal]

  　View Summary

  Objective: The safety, feasibility, and potential functional improvement following the intravenous infusion of mesenchymal stem cells (MSCs) were investigated in patients with chronic severe spinal cord injury (SCI). Methods: The intravenous infusion of autologous MSCs cultured in auto-serum under Good Manufacturing Practices (GMP) was administered to seven patients with chronic SCI (ranging from 1.3 years to 27 years after the onset of SCI). In addition to evaluating feasibility and safety, neurological function was evaluated using the American Spinal Injury Association Impairment Scale (AIS), International Standards for Neurological Classification of Spinal Cord Injury (ISCSCI-92), and Spinal Cord Independence Measure III (SCIM-III). Results: No serious adverse events occurred. Neither CNS tumors, abnormal cell growth, nor neurological deterioration occurred in any patients. While this initial case series was not blinded, significant functional improvements and increased quality of life (QOL) were observed at 90 and 180 days post-MSC infusion compared to pre-infusion status. One patient who had an AIS grade C improved to grade D within six months after MSC infusion. Conclusions: This case series suggests that the intravenous infusion of autologous MSCs is a safe and feasible therapeutic approach for chronic SCI patients. Furthermore, our data showed significant functional improvements and better QOL after MSC infusion in patients with chronic SCI. A blind large-scale study will be necessary to fully evaluate this possibility.

  DOI PubMed

• Intravenous Infusion of Autologous Mesenchymal Stem Cells Expanded in Auto Serum for Chronic Spinal Cord Injury Patients: A Case Series

  Ryosuke Hirota, Masanori Sasaki, Satoshi Iyama, Kota Kurihara, Ryunosuke Fukushi, Hisashi Obara, Tsutomu Oshigiri, Tomonori Morita, Masahito Nakazaki, Takahiro Namioka, Ai Namioka, Rie Onodera, Yuko Kataoka-Sasaki, Shinichi Oka, Mitsuhiro Takemura, Ryo Ukai, Takahiro Yokoyama, Yuichi Sasaki, Tatsuro Yamashita, Masato Kobayashi, Yusuke Okuma, Reiko Kondo, Ryo Aichi, Satoko Ohmatsu, Noritaka Kawashima, Yoichi M. Ito, Masayoshi Kobune, Kohichi Takada, Sumio Ishiai, Toru Ogata, Atsushi Teramoto, Toshihiko Yamashita, Jeffery D. Kocsis, Osamu Honmou

  Journal of Clinical Medicine   13 ( 20 )  2024.10

  　View Summary

  Objective: The safety, feasibility, and potential functional improvement following the intravenous infusion of mesenchymal stem cells (MSCs) were investigated in patients with chronic severe spinal cord injury (SCI). Methods: The intravenous infusion of autologous MSCs cultured in auto-serum under Good Manufacturing Practices (GMP) was administered to seven patients with chronic SCI (ranging from 1.3 years to 27 years after the onset of SCI). In addition to evaluating feasibility and safety, neurological function was evaluated using the American Spinal Injury Association Impairment Scale (AIS), International Standards for Neurological Classification of Spinal Cord Injury (ISCSCI-92), and Spinal Cord Independence Measure III (SCIM-III). Results: No serious adverse events occurred. Neither CNS tumors, abnormal cell growth, nor neurological deterioration occurred in any patients. While this initial case series was not blinded, significant functional improvements and increased quality of life (QOL) were observed at 90 and 180 days post-MSC infusion compared to pre-infusion status. One patient who had an AIS grade C improved to grade D within six months after MSC infusion. Conclusions: This case series suggests that the intravenous infusion of autologous MSCs is a safe and feasible therapeutic approach for chronic SCI patients. Furthermore, our data showed significant functional improvements and better QOL after MSC infusion in patients with chronic SCI. A blind large-scale study will be necessary to fully evaluate this possibility.

  DOI

• Novel method for assessing sinusoidal obstruction syndrome using four‐dimensional computed tomography

  Saori Shimoyama‐Ibuki, Satoshi Iyama, Yoshiya Ohashi, Kento Ono, Yusuke Sugama, Chisa Fujita, Akari Goto, Hiroto Horiguchi, Akihito Fujimi, Takeo Tanaka, Kohichi Takada, Koh‐Ichi Sakata, Masayoshi Kobune

  eJHaem ( Wiley )   2024.07

  　View Summary

  Abstract Introduction To diagnose sinusoidal obstruction syndrome/veno‐occlusive disease (SOS/VOD), transabdominal ultrasonography is usually used to detect hemodynamic changes, but we tried to detect the changes using four‐dimensional computed tomography (4D‐CT). A 42‐year‐old Japanese woman was diagnosed with late‐onset SOS/VOD with transabdominal ultrasonography and was also assessed using 4D‐CT. Method We analyzed the portal vein (PV) contrast effect every 1.5 seconds and plotted the values of the contrast effect. With this graph, we analyzed three hemodynamic parameters. Result We found that these parameters correlated with the patient's status and indicated stasis due to sinusoid constriction. Conclusion 4D‐CT may become a helpful tool to diagnose and follow up with SOS/VOD.

  DOI

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Misc 【 display / non-display 】

Misc 【 display / non-display 】

• Prospective evaluation of alternative donor from unrelated donor and cord blood in adult acute leukemia and myelodysplastic syndrome

  Seitaro Terakura, Tetsuya Nishida, Masashi Sawa, Tomonori Kato, Kotaro Miyao, Yukiyasu Ozawa, Tatsunori Goto, Akio Kohno, Kazutaka Ozeki, Yasushi Onishi, Noriko Fukuhara, Nobuharu Fujii, Hisayuki Yokoyama, Masanobu Kasai, Hiroatsu Iida, Nobuhiro Kanemura, Tomoyuki Endo, Hiroatsu Ago, Makoto Onizuka, Satoshi Iyama, Yuichiro Nawa, Mika Nakamae, Yasuyuki Nagata, Shingo Kurahashi, Yasuo Tomiya, Atsumi Yanagisawa, Ritsuro Suzuki, Yachiyo Kuwatsuka, Yoshiko Atsuta, Koichi Miyamura, Makoto Murata

  Bone Marrow Transplantation ( Springer Science and Business Media LLC )  55 ( 7 ) 1399 - 1409  2020.07  [Refereed]  [International journal]

  　View Summary

  A prospectively registered observational study was conducted to assess the significance of allogeneic hematopoietic stem cell transplantation from highly HLA-matched unrelated donors (UD) and cord blood (CB) on outcomes in adult acute leukemia (AL) and myelodysplastic syndrome (MDS). Between 2007 and 2015, 231 transplant-eligible patients were registered for a phase 2 study of alternative donor transplantation. After registration, a sufficient time period was given to find appropriate UD. Patients received CB transplantation (CBT) if an appropriate UD was unavailable. In total, 119 patients received CBT (106 AL and 13 MDS) and 91 patients received UD transplantation (UDT) (86 AL and 5 MDS). The median age was 39 years in both groups. The primary objective was overall survival (OS); secondary objectives included cumulative incidences of non-relapse mortality (NRM) and relapse, and disease-free survival. Diagnosis, disease status at transplantation, refined disease risk index, and hematopoietic cell transplant-specific comorbidity index did not differ between UDT and CBT. In multivariate analyses, graft source was not a significant risk factor for all objectives. In adjusted analyses, UDT and CBT showed similar OS, NRM, and relapse in this prospective study. CB can be a comparable alternative stem cell source to UD by achieving a timely transplant.

  DOI PubMed

• Prospective Evaluation of Alternative Donor from Unrelated Volunteer Donor and Cord Blood in Adult Acute Leukemia and Myelodysplastic Syndrome: No Difference between Unrelated Donor and Cord Blood

  Seitaro Terakura, Tetsuya Nishida, Masashi Sawa, Tomonori Kato, Kotaro Miyao, Yukiyasu Ozawa, Tatsunori Goto, Akio Kohno, Kazutaka Ozeki, Yasushi Onishi, Noriko Fukuhara, Nobuharu Fujii, Hisayuki Yokoyama, Masanobu Kasai, Hiroatsu Iida, Nobuhiro Kanemura, Tomoyuki Endo, Hiroatsu Ago, Makoto Onizuka, Satoshi Iyama, Yuichiro Nawa, Mika Nakamae, Yasuyuki Nagata, Shingo Kurahashi, Yasuo Tomiya, Atsumi Yanagisawa, Ritsuro Suzuki, Yachiyo Kuwatsuka, Yoshiko Atsuta, Koichi Miyamura, Makoto Murata

  BLOOD ( AMER SOC HEMATOLOGY )  134  2019.11

  Research paper, summary (international conference)  

  　View Summary

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  DOI

• 【悪性黒色腫】 播種性骨髄癌腫症を呈した悪性黒色腫の1例

  澤田 匡秀, 澄川 靖之, 佐藤 さゆり, 菅 裕司, 加藤 潤史, 肥田 時征, 山下 利春, 橋本 亜香利, 井山 諭

  皮膚科の臨床 ( 金原出版(株) )  59 ( 13 ) 1963 - 1966  2017.12

  　View Summary

  79歳女。約2年前に左第4趾に黒色結節を自覚し、徐々に増大した。全切除生検を施行し、病理組織学的所見より悪性黒色腫と診断した。全身検索で他臓器転移を認めず、足趾離断術とセンチネルリンパ節生検を施行した。摘出した4個のリンパ節全てに転移を認めたため、鼠径、外腸骨、閉鎖リンパ節郭清を追加した。郭清したリンパ節に転移はなかった。pT3bN3M0 Stage IIICと診断し、術後化学療法としてDAV-Feron療法を計6クール施行した。以後はフェロン局注療法を継続していたが、術後約3年3ヵ月で突然強い腰痛が出現した。各種画像所見、臨床検査所見、骨髄生検の病理組織所見より、悪性黒色腫による播種性骨髄癌腫症とした。化学療法を施行するも改善なく、入院から19日後に永眠された。

  DOI

• P53-RESTORING SMALL MOLECULE CP-31398 INDUCES APOPTOSIS VIA INDUCTION OF REACTIVE OXIDATIVE SPECIES IN HUMAN MULTIPLE MYELOMA

  Y. Arihara, K. Takada, Y. Kawano, N. Hayasaka, H. Nakamura, S. Kikuchi, Y. Kamihara, K. Murase, H. Ikeda, S. Iyama, T. Sato, K. Miyanishi, M. Kobune, J. Kato

  HAEMATOLOGICA ( FERRATA STORTI FOUNDATION )  102   498 - 498  2017.06

  Research paper, summary (international conference)  

• CD34/EPO-R Double Positive MDS Cells Produce Erythroferrone in Response to Erythropoietin

  Shogo Miura, Masayoshi Kobune, Soushi Ibata, Masahiro Yoshida, Satoshi Iyama, Tsutomu Sato, Kazuyuki Murase, Kohichi Takada, Kaoru Ono, Akari Hashimoto, Ayumi Tatekoshi, Yusuke Kamihara, Yusuke Sugama, Wataru Jomen, Shohei Kikuchi, Hiroshi Ikeda, Hiroto Horiguchi, Yutaka Kawano, Koji Miyanishi, Hiroyuki Kuroda, Masahiro Maeda, Junji Kato

  BLOOD ( AMER SOC HEMATOLOGY )  128 ( 22 )  2016.12

  Research paper, summary (international conference)  

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Awards 【 display / non-display 】

Awards 【 display / non-display 】

• Canon 画論32nd The Best Image，優秀賞

  2024.12  

• 小越章平記念 Best Paer in The Year 2021

  2022.05   Japanese Society for Clinical Nutrition and Metabolism   Possible clinical outcomes using early enteral nutrition in individuals with allogeneic hematopoietic stem cell transplantation: A single-center retrospective study.

  Winner： 井山 諭

Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• Development of new therapy for AML by targeting of neuropeptide-PTH2R system

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2022.04

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  2025.03

   

  小船 雅義, 井山 諭, 池田 博, 後藤 亜香利, 堀口 拓人

• Analysis of the development and pathogenesis of AML/MDS via extracellular vesicles

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2019.04

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  2022.03

   

  Kobune Masayoshi

  Authorship： Coinvestigator(s)

  　View Summary

  The analysis of exome in MDS and AML has revealed the multiple mutations involved in the pathogenesis of these disorders. On the other hand, it has been increasingly focused on the dysfunction of BM microenvironment in the MDS/AML. However, little is known how the dysfunction of BM microenvironment was induced. In this study, high level of miR-7977, miR-8073, and miR-4286 were identified in extracellular vesicles from AML cells. In particular, miR-7977 effect on BM MSCs to reduce the expression of PCBP1 and STK4, resulting in the reduction of multiple mRNA and Hippo signaling, suggesting that it could be involved in the alteration of BM microenvironment favorable to leukemia cell survival. In addition, the possibility of rejuvenation by extracellular vesicles derived from immature cells was investigated. Although the expression of β galactosidase was slightly decreased, no changes of other aging markers were detected. Other strategy may be required for rejuvenation of aging MSCs.

• Efficacy for treating MM with DPP8/9 inhibitor.

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2015.04

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  2018.03

   

  Iyama Satoshi

  Authorship： Principal investigator

  　View Summary

  Recently, the prognosis of patients with multiple myeloma (MM) has considerably improved due to the use of autologous hematopoietic stem cell transplantation and the introduction of new agents such as the immunomodulatory drugs, proteasome inhibitors. However, no curable treatment is available. We have previously shown that the DPP8/9 inhibitor, 1G244, induced MM cells to cell death by apoptosis. Hence, we demonstrated efficacy for treating MM with DPP8/9 inhibitor.

• Novel strategy against GVHD using NB-UVB with expansion of Treg cells

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2013.04

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  2016.03

   

  Sato Tsutomu, Iyama Satoshi, Kawano Yutaka

  Authorship： Coinvestigator(s)

  　View Summary

  Narrowband ultraviolet B (NB-UVB) has been widely used in dermatological phototherapy. As for the application of NB-UVB phototherapy to GVHD, we previously reported that it was highly efficacious for cutaneous lesions of acute GVHD (aGVHD) and that expansion of regulatory T (Treg) cells induced by NB-UVB might be one of the mechanisms. In order to examine whether NB-UVB irradiation through expansion of Treg cells is effective for the treatment of not only cutaneous aGVHD but also aGVHD of inner organs such as the intestine or liver, we conducted experiments in which a murine lethal aGVHD model, characterized by severe involvement of the intestine, were irradiated with NB-UVB. We found that NB-UVB irradiation improved the clinical score and survival rate. The numbers of infiltrating Treg cells in inflamed tissue of the intestine and those in spleen were increased in mice treated with NB-UVB.

• Establishment of iron chelation therapy to inhibit the development of MDS

  Grant-in-Aid for Challenging Exploratory Research

  Project Year :

  2012.04

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  2015.03

   

  KOBUNE Masayoshi, KIKUCHI Shohei, IYAMA Satoshi, KATO Junji

  Authorship： Coinvestigator(s)

  　View Summary

  Most MDS patients eventually require red RBC transfusions for anemia and consequently develop iron overload. Excess free iron in cells catalyzes generation of reactive oxygen species that cause oxidative stress, including oxidative DNA damage. However, it is uncertain how iron-mediated oxidative stress affects the pathophysiology of MDS. We analyzed 8-OHdG levels in peripheral blood mononuclear cells (PBMC) obtained from MDS patients before and after iron chelator,deferasirox, administration. We showed that the 8-OHdG levels in MDS patients were significantly higher than those in healthy volunteers and were positively correlated with SF and chromosomal abnormalities. Importantly, the 8-OHdG levels in PBMC of MDS patients significantly decreased after deferasirox administration, suggesting that iron chelation reduced oxidative DNA damage. Thus, excess iron could contribute to the pathophysiology of MDS and iron chelation therapy could improve the oxidative DNA damage in MDS patients.

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