2013 Fiscal Year Final Research Report
Analysis of the resistant mechanism of AML stem cells for tyrosine kinase inhibitor in bone marrow microenvironment
| Project/Area Number |
23591537
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Okayama University (2012-2013)
Nagoya University (2011) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Yasuhide 群馬県衛生環境研究所, 研究企画係, 研究員 (30238133)
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| Project Period (FY) |
2011 – 2013
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| Keywords | AML / TKI / MSC / drug resistance / 抗メチル化薬 / HDAC阻害剤 |
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| Research Abstract |
The mechanism of drug resistance for Tyrosine kinase inhibitor (TKI) in AML cells remains unkown. AML cells showed the drug resistance in coculture model with mesenchimal stroma cells(MSCs). AML cells became more resistant for TKI in direct contact with MSC than in floating condition. For this reason, adhesion molecule such as integrin, or several cytokines and chemokines affected the up-regulation of AKT, MAPK and JAK/STAT signaling pathway. When AML cells were cocultured with MSC for more than 4 weeks, the fraction of side population increased and showed TKI resistance. To overcome this drug resistance, we found the synergistic effect in TKI with PI3K/mROR/AKT inhibitor or in TKI with JAK/STAT inhibitor.
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Research Products
(21 results)
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[Journal Article] ABL kinase mutation and relapse in 4 pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia cases2014
Author(s)
Aoe M, Shimada A, Muraoka M, Washio K, Nakamura Y, Takahashi T, Imada M, Watanabe T, Okada K, Nishiuchi R, Ishida T, Miyamura T, Chayama K, Shibakura M, Oda M, Morishima T.
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Journal Title
Int J Hematol
Volume: 99
Pages: 609-15
DOI
Peer Reviewed
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[Journal Article] RUNX1 mutation associated with clonal evolution in relapsed pediatric acute myeloid leukemia with t(16;21)(p11;q22)2014
Author(s)
Ismael O, Shimada A, Elmandi S, Elshazley M, Muramatsu H, Hama A, Takahashi Y, Yamada M, Yamashita Y, Horibe K, Kojima S.
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Journal Title
Int J Hematol
Volume: 99
Pages: 169-174
DOI
Peer Reviewed
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[Journal Article] Appropriate dose reduction in induction therapy is essential for the treatment of infants with acute myeloid leukemia: a report from the Japanese Pediatric Leukemia/Lymphoma Study Group2013
Author(s)
Tomizawa D, Tawa A, Watanabe T, Saito AM, Kudo K, Taga T, Iwamoto S, Shimada A, Terui K, Moritake H, Kinoshita A, Takahashi H, Nakayama H, Kiyokawa N, Isoyama, K, Mizutani S, Hara J, Horibe K, Nakahata T, Adachi S.
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Journal Title
Int J Hematol
Volume: 98
Pages: 578-588
DOI
Peer Reviewed
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[Journal Article] WT1 mutation in pediatric patients with acute myeloid leukemia: a report from the Japanese Childhood AML Cooperative Study Group2013
Author(s)
Sano H, Shimada A, Tabuchi K, Taki T, Murata C, Park MJ, Ohki K, Sotomatsu M, Adachi S, Tawa A, Kobayashi R, Horibe K, Tsuchida M, Hanada R, Ichiro Tsukimoto I, Hayashi Y.
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Journal Title
Int J Hematol
Volume: 98
Pages: 437-445
DOI
Peer Reviewed
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[Journal Article] Excess treatment reduction including anthracyclines results in higher incidence of relapse in core binding factor acute myeloid leukemia in children2013
Author(s)
Tomizawa D, Tawa A, Watanabe T, Saito AM, Kudo K, Taga T, Iwamoto S, Shimada A, Terui K, Moritake H, Kinoshita A, Takahashi H, Nakayama H, Koh K, Kigasawa H, Kosaka Y, Miyachi H, Horibe K, Nakahata T, Adachi S.
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Journal Title
Leukemia
Volume: 27
Pages: 2413-2416
DOI
Peer Reviewed
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[Journal Article] High WT1 mRNA expression after induction chemotherapy and FLT3-ITD have prognostic impact in pediatric acute myeloid leukemia: A study of the Japanese Childhood AML Cooperative Study Group2012
Author(s)
Shimada A, Taki T, Koga D, Tabuchi K, Tawa A, Hanada R, Tsuchida M, Horibe K, Tsukimoto I, Adachi S, Kojima S, Hayashi Y.
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Journal Title
Int J Hematol
Volume: 96
Pages: 469-76
DOI
Peer Reviewed
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[Journal Article] Outcome in 146 patients with pediatric acute myeloid leukemia treated with AML99 protocol in the period 2003-2006 in Japan Association of Childhood Leukemia Study (JACLS)2012
Author(s)
Imamura T, Iwamoto S, Kanai R, Shimada A, Terui K, Ohsugi Y, Kobayashi R, Tawa A, Kosaka Y, Kato K, Hari H, Horibe K, Oda M, Adachi S, for the Japan Association of Childhood Leukemia Study (JACLS).
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Journal Title
Br J Haematol
Volume: 159
Pages: 204-10
DOI
Peer Reviewed
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[Journal Article] Clinical Characteristics and Outcome of Refractory/Relapsed Myeloid Leukemia in Children with Down Syndrome2012
Author(s)
Taga T, Saito M. A, Kudo K, Tomizawa D, Terui K, Moritake H, Kinoshita A, Iwamoto S, Nakayama H, Takahashi H, Tawa A, Shimada A, Taki T, Kigasawa H, Koh K, and Adachi S.
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Journal Title
Blood
Volume: 120
Pages: 1810-5
DOI
Peer Reviewed
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[Journal Article] RAS mutations are frequent in FAB type M4 and M5 of acute myeloid leukemia, and related to late relapse: A study of the Japanese Childhood AML Cooperative Study Group2012
Author(s)
Sano H , Shimada A, Taki T, Murata C, Park MJ, Sotomatsu M, Tabuchi K, Tawa A, Kobayashi R, Horibe K, Tsuchida M, Hanada R, Tsukimoto I, Hayashi Y
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Journal Title
Int J Hematol
Volume: 95
Pages: 509-15
DOI
Peer Reviewed
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[Journal Article] DNMT3A mutations are rare in childhood acute myeloid leukaemia, myelodysplastic syndromes and juvenile myelomonocytic leukaemia2012
Author(s)
Shiba N, Taki T, Park MJ, Shimada A, Sotomatsu M, Adachi S, Tawa A, Horibe K, Tsuchida M, Hanada R, Tsukimoto I, Arakawa H, Hayashi Y.
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Journal Title
Br J Haematol
Volume: 156
Pages: 413-4
DOI
Peer Reviewed
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[Journal Article] Molecular lesions in childhood and adult acute megakaryoblastic leukemia2012
Author(s)
Hama A, Muramatsu H, Makishima H, Sugimoto Y, Szpurka H, Jasek M, O'Keefe C, Takahashi Y, Sakaguchi H, Doisaki S, Shimada A, Watanabe N, Kato K, Kojima S, Maciejewski JP.
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Journal Title
Br J. Haematol
Volume: 156
Pages: 316-25
DOI
Peer Reviewed
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