研究者詳細 - 嶋　晴子

嶋　晴子 (シマ　ハルコ)

Shima, Haruko

写真a

所属（所属キャンパス）: 医学部小児科学教室（信濃町）

職名: 助教（有期）

このページの先頭へ▲

経歴【表示／非表示】

2003年05月

-

2009年03月

慶應義塾大学医学部, 小児科学, 初期研修医/専修医
2009年04月

-

2011年03月

国立がん研究センター研究所, 造血器腫瘍研究分野, リサーチレジデント/がん特別研究員
2012年04月

-

継続中

慶應義塾大学医学部, 小児科, 助教

このページの先頭へ▲

学歴【表示／非表示】

1997年04月

-

2003年03月

秋田大学, 医学部, 医学科

大学, 卒業
2005年04月

-

2009年03月

慶應義塾大学, 医学研究科, 内科系小児科学

大学院, 修了, 博士

このページの先頭へ▲

学位【表示／非表示】

医学博士, 慶應義塾大学, 課程, 2009年03月

このページの先頭へ▲

論文【表示／非表示】

Discontinuation of Tyrosine Kinase Inhibitor in Children with Chronic Myeloid Leukemia (JPLSG STKI-14 study)

Shima H., Kada A., Tanizawa A., Yuza Y., Watanabe A., Ito M., Uryu H., Koh K., Imai C., Yoshida N., Koga Y., Fujita N., Saito A.M., Adachi S., Ishii E., Shimada H.

Blood （Blood) 134 （ 1 ） 2019年11月

　概要を見る

© 2019 by The American Society of Hematology. DISCLOSURES: Kada: Bayer Yakuhin: Other: personal fees for a member of independent data monitoring committee of clinical trials, outside of the submitted work.. Imai:Juno Therapeutics: Patents & Royalties.
- Access to Document (DOI)
Ring1A and Ring1B inhibit expression of Glis2 to maintain murine MOZ-TIF2 AML stem cells

Shima H., Takamatsu-Ichihara E., Shino M., Yamagata K., Katsumoto T., Aikawa Y., Fujita S., Koseki H., Kitabayashi I.

Blood （Blood) 131 （ 16 ） 1833 - 1845 2018年04月

ISSN 00064971

　概要を見る

© 2018 by The American Society of Hematology. Eradication of chemotherapy-resistant leukemia stem cells is expected to improve treatment outcomes in patients with acute myelogenous leukemia (AML). In a mouse model of AML expressing the MOZ-TIF2 fusion, we found that Ring1A and Ring1B, components of Polycomb repressive complex 1, play crucial roles in maintaining AML stem cells. Deletion of Ring1A and Ring1B (Ring1A/B) from MOZ-TIF2 AML cells diminished self-renewal capacity and induced the expression of numerous genes, including Glis2. Overexpression of Glis2 caused MOZ-TIF2 AML cells to differentiate into mature cells, whereas Glis2 knockdown in Ring1A/B-deficient MOZ-TIF2 cells inhibited differentiation. Thus, Ring1A/B regulate and maintain AML stem cells in part by repressing Glis2 expression, which promotes their differentiation. These findings provide new insights into the mechanism of AML stem cell homeostasis and reveal novel targets for cancer stem cell therapy.
- Access to Document (DOI)
Bromodomain-PHD finger protein 1 is critical for leukemogenesis associated with MOZ-TIF2 fusion

Shima Haruko, Yamagata Kazutsune, Aikawa Yukiko, Shino Mika, Koseki Haruhiko, Shimada Hiroyuki, Kitabayashi Issay

International Journal of Hematology 99 （ 1 ） 21 - 31 2014年

ISSN 0925-5710

　概要を見る

Chromosomal translocations that involve the monocytic leukemia zinc finger (MOZ) gene are typically associated with human acute myeloid leukemia (AML) and often predict a poor prognosis. Overexpression of HOXA9, HOXA10, and MEIS1 was observed in AML patients with MOZ fusions. To assess the functional role of HOX upregulation in leukemogenesis by MOZ-TIF2, we focused on bromodomain-PHD finger protein 1 (BRPF1), a component of the MOZ complex that carries out histone acetylation for generating and maintaining proper epigenetic programs in hematopoietic cells. Immunoprecipitation analysis showed that MOZ-TIF2 forms a stable complex with BRPF1, and chromatin immunoprecipitation analysis showed that MOZ-TIF2 and BRPF1 interact with HOX genes in MOZ-TIF2-induced AML cells. Depletion of BRPF1 decreased the MOZ localization on HOX genes, resulting in loss of transformation ability induced by MOZ-TIF2. Furthermore, mutant MOZ-TIF2 engineered to lack histone acetyltransferase activity was incapable of deregulating HOX genes as well as initiating leukemia. These data indicate that MOZ-TIF2/BRPF1 complex upregulates HOX genes mediated by MOZ-dependent histone acetylation, leading to the development of leukemia. We suggest that activation of BRPF1/HOX pathway through MOZ HAT activity is critical for MOZ-TIF2 to induce AML. © The Japanese Society of Hematology 2013.
- Access to Document (DOI)
Distinct impact of imatinib on growth at prepubertal and pubertal ages of children with chronic myeloid leukemia

Shima Haruko, Tokuyama Mika, Tanizawa Akihiko, Tono Chikako, Hamamoto Kazuko, Muramatsu Hideki, Watanabe Akihiro, Hotta Noriko, Ito Masaki, Kurosawa Hidemitsu, Kato Koji, Tsurusawa Masahito, Horibe Keizo, Shimada Hiroyuki

Journal of Pediatrics 159 （ 4 ） 676 - 681 2011年10月

ISSN 0022-3476

　概要を見る

Objective: To determine the extent of growth impairment resulting from imatinib treatment in children with chronic myeloid leukemia (CML). Study design: Clinical records of 48 chronic-phase CML children administered imatinib as the first-line therapy between 2001 and 2006 were analyzed retrospectively. Cumulative change in height was assessed using the height height-SDS and converted height data from age- and sex-adjusted Japanese norms. Results: A decrease in height-SDS was observed in 72.9% of children, with a median maximum reduction in height-SDS of 0.61 during imatinib treatment. Median follow-up time was 34 months (range, 10-88 months). Growth impairment was seen predominantly in children who started imatinib at a prepubertal age compared with those who started at pubertal age. Growth velocity tended to recuperate in prepubertal children with growth impairment, as they reached pubertal age, suggesting that imatinib had little impact on growth during puberty. Conclusions: Growth impairment was a major adverse effect of long-term imatinib treatment in children with CML. We report the distinct inhibitory effect of imatinib on growth in prepubertal and pubertal children with CML. We should be aware of growth deceleration in children, especially in young children given imatinib before puberty and subjected to prolonged exposure. © 2011 Mosby Inc. All rights reserved.
- Access to Document (DOI)
Acquisition of G₀ state by CD34-positive cord blood cells after bone marrow transplantation

Shima Haruko, Takubo Keiyo, Tago Naoko, Iwasaki Hiroko, Arai Fumio, Takahashi Takao, Suda Toshio

Experimental Hematology 38 （ 12 ） 1231 - 1240 2010年12月

ISSN 0301-472X

　概要を見る

Objective: Hematopoietic stem cells are kept in a quiescent state in the hypoxic area of the bone marrow, which is essential for hematopoietic stem cell maintenance. However, when and how hematopoietic stem cells acquire their hypoxic state and maintain quiescence has not been fully elucidated. The aim of this study was to understand this process in human hematopoietic stem cells after bone marrow transplantation. Materials and Methods: Human CD34-positive cord blood cells were transplanted into nonobese diabetic/severe combined immunodeficient interleukin-2 receptor γ chain knockout mice. Cell cycle and hypoxia assay analyses were performed, to identify changes in the characteristics of human hematopoietic stem cells following transplantation. Quantitative real-time reverse transcription polymerase chain reaction analysis was used to analyze the transcriptional changes accompanying this transition. Results: Engrafted primitive lineage-negative CD34-positive CD38-negative cells acquired hypoxic state and quiescence in the recipient bone marrow between 4 and 8 weeks, and between 8 and 12 weeks after transplantation, respectively. During 4 and 8 weeks after transplantation, changes in the transcription levels of G₀ regulatory factors, such as CCNC and RBL1, and stem cell regulators, such as Flt3, were also seen, which may be related to the characteristic changes in the cell cycle or oxygenation state. Conclusions: Behavioral changes of hematopoietic stem cells in their cell cycle and oxygenation state during and after bone marrow engraftment may provide insights into hematopoietic stem cell regulation, mediating the improvement of clinical hematopoietic stem cell transplantation protocols and the eradication of leukemia stem cells. © 2010 ISEH - Society for Hematology and Stem Cells.
- Access to Document (DOI)