研究者詳細 - 増子　正義

Refinement of the Glasgow Prognostic Score as a pre-transplant risk assessment for allogeneic hematopoietic cell transplantation 査読

Yasuhiko Shibasaki, Tatsuya Suwabe, Takayuki Katagiri, Tomoyuki Tanaka, Takashi Ushiki, Kyoko Fuse, Naoko Sato, Toshio Yano, Takashi Kuroha, Shigeo Hashimoto, Miwako Narita, Tatsuo Furukawa, Hirohito Sone, Masayoshi Masuko

International Journal of Hematology 108 ( 3 ) 1 - 8 2018年5月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Springer Tokyo

The Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) is a widely used tool for pre-transplant risk assessment. Allogeneic hematopoietic cell transplantation (HCT) is performed on patients with diverse backgrounds, highlighting the need for other predictors to complement the HCT-CI and support bedside decision-making. There is a strong body of evidence supporting the use of pre-transplant serum ferritin (SF) in risk assessments of allogeneic HCT. We additionally found that the Glasgow Prognostic Score (GPS), which assesses inflammatory biomarkers and predicts survival of patients with solid organ malignancies, is a useful predictive marker for overall survival (OS) and non-relapse mortality (NRM) in allogeneic HCT, independent of HCT-CI and SF. In this study, we refined the GPS by adding pre-transplant SF to improve its prognostic ability and enable better stratification
we call this revised index the HCT-specific revised Glasgow Prognostic Score (HCT-GPS). We observed that the HCT-GPS more accurately predicted NRM and early-term OS than the GPS. Moreover, the HCT-GPS provides an independent prognostic factor adjusted for the HCT-CI and disease status, and stratifies patients into four risk groups by OS and NRM. Thus, the HCT-GPS is a useful index for predicting early-term complications after allogeneic HCT in patients with hematopoietic diseases.

DOI： 10.1007/s12185-018-2463-x

Scopus

GDP療法がtriple-hit lymphomaの救援療法として有効であった1例

水戸部正樹, 河本啓介, 鈴木隆晴, 田村秀, 小堺貴司, 難波亜矢子, 諏訪部達也, 笠見卓哉, 田中智之, 布施香子, 柴崎康彦, 増子正義, 曽根博仁, 大島孝一, 瀧澤淳

臨床血液 59 ( 5 ) 620 - 621 2018年5月

MAGI-1 expression is decreased in several types of human T-cell leukemia cell lines, including adult T-cell leukemia 査読

Takashi Kozakai, Masahiko Takahashi, Masaya Higuchi, Toshifumi Hara, Kousuke Saito, Yuetsu Tanaka, Masayoshi Masuko, Jun Takizawa, Hirohito Sone, Masahiro Fujii

International Journal of Hematology 107 ( 3 ) 337 - 344 2018年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Springer Tokyo

Membrane-associated guanylate kinase with inverted orientation protein 1 (MAGI-1) is a cytoplasmic scaffold protein that interacts with various signaling molecules
it negatively controls the cell growth of various types of cells and positively controls cell–cell interaction. In T cells, MAGI-1 has been shown to inhibit Akt activity through its interaction with PTEN and MEK1. In this study we found that MAGI-1 expression is decreased in multiple (9 out of 15) human T-cell leukemia cell lines, including adult T-cell leukemia (ATL), T-cell acute lymphoblastic leukemia and chronic T-cell lymphocytic leukemia. The overexpression of MAGI-1 protein in a MAGI-1-low ATL cell line reduced cellular growth. While the overexpression of MAGI-1 protein in a MAGI-1-low ATL cell line reduced the Akt and MEK activities, the knockdown of MAGI-1 in a MAGI-1-high ATL cell line augmented the Akt and MEK activities. Collectively, the findings of the present study suggest that the decreased expression of MAGI-1 in human T cells contributes to the development of several types of T-cell leukemia, partly through the stimulation of the Akt and MEK pathways.

DOI： 10.1007/s12185-017-2359-1

Scopus

Outcomes after allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia harboring t(7;11)(p15;p15) 査読

Kaito Harada, Noriko Doki, Jun Aoki, Jinichi Mori, Shinichiro Machida, Masayoshi Masuko, Naoyuki Uchida, Yuho Najima, Takahiro Fukuda, Heiwa Kanamori, Hiroyasu Ogawa, Shuichi Ota, Kazuei Ogawa, Satoshi Takahashi, Masanobu Kasai, Akio Maeda, Koji Nagafuji, Toshiro Kawakita, Tatsuo Ichinohe, Yoshiko Atsuta

Haematologica 103 ( 2 ) e69 - e72 2018年1月

The Glasgow Prognostic Score as a pre-transplant risk assessment for allogeneic hematopoietic cell transplantation 査読

Yasuhiko Shibasaki, Tatsuya Suwabe, Takayuki Katagiri, Tomoyuki Tanaka, Hironori Kobayashi, Kyoko Fuse, Takashi Ushiki, Naoko Sato, Toshio Yano, Takashi Kuroha, Shigeo Hashimoto, Miwako Narita, Tatsuo Furukawa, Hirohito Sone, Masayoshi Masuko

CLINICAL TRANSPLANTATION 31 ( 11 ) 2017年11月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WILEY

Evaluation methods, such as scoring systems for predicting complications in advance, are necessary for determining the adaptation of allogeneic hematopoietic cell transplantation (HCT) and selecting appropriate conditioning regimens. The Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI), which is based on functions of main organs, is a useful tool for pre-transplant risk assessments and has been widely applied in determining treatment strategies for patients with hematological diseases. However, as allogeneic HCT is performed on patients with diverse backgrounds, another factor, which reinforces the HCT-CI, is required to evaluate pre-transplant risk assessments. The Glasgow Prognostic Score (GPS), which assesses the combined C-reactive protein and albumin, was reported to predict survival of patients with solid-organ malignancies independently of receiving chemo/radiotherapy and stages of cancer. In this study, we applied the GPS for pre-transplant risk assessments for allogeneic HCT. The GPS successfully stratified the patients into three risk groups of overall survival (OS) and non-relapse mortality (NRM). Moreover, the GPS could predict outcomes independently of the HCT-CI for OS and NRM in multivariate analysis. The GPS is considered to be a useful tool and reinforces the HCT-CI for determining adaptation of allogeneic HCT for patients with hematopoietic neoplasms.

DOI： 10.1111/ctr.13103

Internal deletion of BCOR reveals a tumor suppressor function for BCOR in T lymphocyte malignancies 査読

Tomoyuki Tanaka, Yaeko Nakajima-Takagi, Kazumasa Aoyama, Shiro Tara, Motohiko Oshima, Atsunori Saraya, Shuhei Koide, Sha Si, Ichiro Manabe, Masashi Sanada, Manabu Nakayama, Masayoshi Masuko, Hirohito Sone, Haruhiko Koseki, Atsushi Iwama

JOURNAL OF EXPERIMENTAL MEDICINE 214 ( 10 ) 2901 - 2913 2017年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ROCKEFELLER UNIV PRESS

Recurrent inactivating mutations have been identified in various hematological malignancies in the X-linked BCOR gene encoding BCL6 corepressor (BCOR); however, its tumor suppressor function remains largely uncharacterized. We generated mice missing Bcor exon 4, expressing a variant BCOR lacking the BCL6-binding domain. Although the deletion of exon 4 in male mice (Bcor(Delta E4/gamma)) compromised the repopulating capacity of hematopoietic stem cells, Bcor(Delta E4/gamma) thymocytes had augmented proliferative capacity in culture and showed a strong propensity to induce acute T-cell lymphoblastic leukemia (T-ALL), mostly in a Notch-dependent manner. Myc, one of the critical NOTCH1 targets in T-ALL, was highly up-regulated in Bcor(Delta E4/gamma) T-ALL cells. Chromatin immunoprecipitation/DNA sequencing analysis revealed that BCOR was recruited to the Myc promoter and restrained its activation in thymocytes. BCOR also targeted other NOTCH1 targets and potentially antagonized their transcriptional activation. Bcl6-deficient thymocytes behaved in a manner similar to Bcor(Delta E4/gamma) thymocytes. Our results provide the first evidence of a tumor suppressor role for BCOR in the pathogenesis of T lymphocyte malignancies.

DOI： 10.1084/jem.20170167

抗原特異的細胞傷害性T細胞(CTL)の増幅と機能の検討

小川彩空, 増子正義, 後藤若奈, 内山孝由, 橋本誠雄, 柴崎康彦, 瀧澤淳, 成田美和子

日臨技北日本支部医学検査学会抄録集 6回 128 - 128 2017年10月

Functional dissection of hematopoietic stem cell populations with a stemness-monitoring system based on NS-GFP transgene expression 査読

Mohamed A. E. Ali, Kyoko Fuse, Yuko Tadokoro, Takayuki Hoshii, Masaya Ueno, Masahiko Kobayashi, Naho Nomura, Ha Thi Vu, Hui Peng, Ahmed M. Hegazy, Masayoshi Masuko, Hirohito Sone, Fumio Arai, Atsushi Tajima, Atsushi Hirao

SCIENTIFIC REPORTS 7 ( 1 ) 11442 2017年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：NATURE PUBLISHING GROUP

Hematopoietic stem cells (HSCs) in a steady state can be efficiently purified by selecting for a combination of several cell surface markers; however, such markers do not consistently reflect HSC activity. In this study, we successfully enriched HSCs with a unique stemness-monitoring system using a transgenic mouse in which green florescence protein (GFP) is driven by the promoter/enhancer region of the nucleostemin (NS) gene. We found that the phenotypically defined long-term (LT)-HSC population exhibited the highest level of NS-GFP intensity, whereas NS-GFP intensity was strongly downregulated during differentiation in vitro and in vivo. Within the LT-HSC population, NS-GFPhigh cells exhibited significantly higher repopulating capacity than NS-GFPlow cells. Gene expression analysis revealed that nine genes, including Vwf and Cdkn1c (p57), are highly expressed in NS-GFPhigh cells and may represent a signature of HSCs, i.e., a stemness signature. When LT-HSCs suffered from remarkable stress, such as transplantation or irradiation, NS-GFP intensity was downregulated. Finally, we found that high levels of NS-GFP identified HSC-like cells even among CD34(+) cells, which have been considered progenitor cells without long-term reconstitution ability. Thus, high NS-GFP expression represents stem cell characteristics in hematopoietic cells, making this system useful for identifying previously uncharacterized HSCs.

DOI： 10.1038/s41598-017-11909-3

Successful 5-azacytidine treatment of myeloid sarcoma and leukemia cutis associated with myelodysplastic syndrome A case report and literature review 査読

Takayuki Katagiri, Takashi Ushiki, Masayoshi Masuko, Tomoyuki Tanaka, Shukuko Miyakoshi, Kyoko Fuse, Yasuhiko Shibasaki, Jun Takizawa, Sadao Aoki, Hirohito Sone

MEDICINE 96 ( 36 ) e7975 2017年9月

記述言語：英語出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS

Rationale: Myeloid sarcoma (MS) and leukemia cutis (LC) are extramedullary tumors comprising myeloid blasts. They can occur de novo or concurrently with hematological disorders, usually acute myeloid leukemia (AML). AML chemotherapy is generally the initial therapy for MS and LC, and hematopoietic stem cell transplantation (HSCT) can be considered as additional therapy. However, treatment for older patients who are unable to continue intensive chemotherapy is not currently standardized.
Patientconcerns: A 71-year-old Japanese woman was diagnosed with multiple MSs associated with myelodysplastic syndrome (MDS), using bone marrow aspiration and lymph node biopsy.
Diagnoses: Additionally, LC was diagnosed by skin biopsy. Extramedullary MS and LC lesions were formed by massive infiltration of myeloblastic cells.
Interventions: Twenty courses of 5-azacytidine (5-Aza) were administrated as maintenance therapy after induction therapy with daunorubicin and cytarabine.
Outcomes: Myeloblasts decreased in the bone marrow and the LC disappeared after induction therapy. The MSs completely disappeared, except for the palatine tonsil lesion, after 5-Aza maintenance therapy. 5-Aza treatment provided long-term partial response for more than 21 months.
Lessons: 5-Aza was well tolerated and may be a good option for the treatment of MS and LC associated with MDS, especially in older patients who cannot receive HSCT.

DOI： 10.1097/MD.0000000000007975

移植前予後予測モデルとしての同種造血細胞移植特異的Glasgow Prognostic Score(HCT specific Glasgow Prognostic Score as a new predictive tool for pre-transplant risk assessments)

Shibasaki Yasuhiko, Suwabe Tatsuya, Katagiri Takayuki, Tanaka Tomoyuki, Kobayashi Hironori, Fuse Kyoko, Ushiki Takashi, Narita Miwako, Sone Hirohito, Masuko Masayoshi

臨床血液 58 ( 9 ) 1547 - 1547 2017年9月

Phase II study of intrabone single unit cord blood transplantation for hematological malignancies. 査読国際誌

Makoto Murata, Yoshinobu Maeda, Masayoshi Masuko, Yasushi Onishi, Tomoyuki Endo, Seitaro Terakura, Yuichi Ishikawa, Chisako Iriyama, Yoko Ushijima, Tatsunori Goto, Nobuharu Fujii, Mitsune Tanimoto, Hironori Kobayashi, Yasuhiko Shibasaki, Noriko Fukuhara, Yoshihiro Inamoto, Ritsuro Suzuki, Yoshihisa Kodera, Tadashi Matsushita, Hitoshi Kiyoi, Tomoki Naoe, Tetsuya Nishida

Cancer science 108 ( 8 ) 1634 - 1639 2017年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

The outcomes of cord blood transplantation with non-irradiated reduced-intensity conditioning for hematological malignancies need to be improved because of graft failure and delayed engraftment. Intrabone infusion of cord blood cells has the potential to resolve the problems. In this phase II study, 21 adult patients with hematological malignancy received intrabone transplantation of serological HLA-A, B, and DR ≥4/6 matched single cord blood with a median number of cryopreserved total nucleated cells of 2.7 × 107 /kg (range, 2.0-4.9 × 107 /kg) following non-irradiated fludarabine-based reduced-intensity conditioning. Short-term methotrexate and tacrolimus were given as graft-versus-host disease prophylaxis, and granulocyte colony-stimulating factor was given after transplantation. No severe adverse events related to intrabone injection were observed. The cumulative incidences of neutrophils ≥0.5 × 109 /L, reticulocytes ≥1%, and platelets ≥20 × 109 /L recoveries were 76.2%, 71.4%, and 76.2%, respectively, with median time to recoveries of 17, 28, and 32 days after transplantation, respectively. The probability of survival with neutrophil engraftment on day 60 was 71.4%, and overall survival at 1 year after transplantation was 52.4%. The incidences of grade II-IV and III-IV acute graft-versus-host disease were 44% and 19%, respectively, with no cases of chronic graft-versus-host disease. The present study showed the safety of direct intrabone infusion of cord blood. Further analysis is required to confirm the efficacy of intrabone single cord blood transplantation with non-irradiated reduced-intensity conditioning for adult patients with hematological malignancy. This study was registered with UMIN-CTR, number 000000865.

DOI： 10.1111/cas.13291

Donor Killer Immunoglobulin-Like Receptor Haplotype B/x Induces Severe Acute Graft-versus-Host Disease in the Presence of Human Leukocyte Antigen Mismatch in T Cell-Replete Hematopoietic Cell Transplantation 査読

Ryosuke Hosokai, Masayoshi Masuko, Yasuhiko Shibasaki, Akihiko Saitoh, Tatsuo Furukawa, Chihaya Imai

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION 23 ( 4 ) 606 - 611 2017年4月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCIENCE INC

Natural killer cells have been identified as a mediator of alloimmune reactions in allogeneic hematopoietic stem cell transplantation (HSCT). Killer immunoglobulin-like receptors (KIRs) are an important determinant of natural killer cell function. The relationship between KIR genotypes/haplotypes and clinical outcomes of allogeneic HSCT is complex and inconsistent among several reports. We assessed the clinical impact of KIR haplotype on T cell-replete allogeneic HSCTs performed in a single Japanese center for hematological malignancies (n = 106). A comparison of 2 groups, donor haplotypes A/A and B/x, revealed no significant differences in overall survival, relapse, and nonrelapse mortality. However, grade III to IV acute graft-versus-host disease (GVHD) occurred significantly more frequently in the KIR haplotype B/x group (A/A versus B/x: 4.9% versus 20.0%; P=.02). This was even more evident when HLA mismatch was present. The highest incidences of grade II to IV and grade III to IV acute GVHD were observed in patients who received allografts from HLAmismatched donors with KIR haplotype B/x. These data highlight the importance of KIR genotyping in donor matching, especially when HLA mismatch allogeneic grafting is planned. (C) 2017 American Society for Blood and Marrow Transplantation.

DOI： 10.1016/j.bbmt.2016.12.638