Overexpression of RUNX1 short isoform induced by epigenetic dysregulation in the development of myelodysplastic/myeloproliferative neoplasms (MDS/MPN)
| Project/Area Number |
15K09460
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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 |
Hematology
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| Research Institution | Tokyo University of Pharmacy and Life Science (2016-2017)
Juntendo University (2015) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
原田 結花 文京学院大学, 保健医療技術学部, 教授 (50379848)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | RUNX1 / 慢性骨髄単球性白血病（CMML） / MDS/MPN / スプライシング因子 / BMTモデル / アイソタイプ |
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| Outline of Final Research Achievements |
RUNX1 mutations have been shown to contribute to the development of myeloid neoplasms and are frequently identified in patients with myelodysplastic/myeloproliferative neoplasms (MDS/MPN) including chronic monocytic leukemia (CMML). The RUNX1 gene has several isoforms. We focused on both functional full-length isoforms RUNX1b and the short isoform RUNX1a. RUNX1a has a dominant negative effect on RUNX1b. We quantified expression levels of RUNX1 isoforms in CD34+ cells from patients with MDS/MPN. We found that RUNX1a was overexpressed in MDS/MPN patients, and that these levels of expression increased as the disease progressed. Furthermore, the aberrant splicing resulting in RUNX1a was shown to be caused by splicing factor mutations that are frequently detected in MDS/MPN. We demonstrated for the first time that in addition to RUNX1 mutations, overexpression of RUNX1a induced by splicing factor mutations may have an important role in disease progression in MDS/MPN patients.
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Report
(4 results)
Research Products
(69 results)
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[Journal Article] Spectrum of clinical and genetic features of patients with inherited platelet disorder with suspected predisposition to hematological malignancies: a nationwide survey in Japan.2016
Author(s)
Yoshimi A, Toya T, Nannya Y, Takaoka K, Kirito K, Ito E, Nakajima H, Hayashi Y, Takahashi T, moriya-Saito A, Suzuki K, Harada H, Komatsu N, Usuki K, Ixhikawa M, Kurokawa M.
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Journal Title
Annals of Oncology
Volume: 27
Issue: 5
Pages: 887-895
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Genetic basis of myeloid transformation in familial platelet disorder/acute myeloid leukemia patients with haploinsufficient RUNX1 allele2016
Author(s)
Sakurai M, Kasahara H, Yoshida K, Yoshimi A, Kunimoto H, Watanabe N, Shiraishi Y, Chiba K, Tanaka H, Harada Y, Harada H, Kawakita T, Kurokawa M, Miyano S, Takahashi S, Ogawa S, Okamoto S, Nakajima H
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Journal Title
Blood Cancer J
Volume: 6
Issue: 2
Pages: e392-e392
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Spectrum of clinical and genetic features of patients with inherited platelet disorder with suspected predisposition to hematological malignancies: a nationwide survey in Japan2016
Author(s)
Yoshimi A, Toya T, Nannya Y, Takaoka K, Kirito K, Ito E, Nakajima H, Hayashi Y, Takahashi T, Moriya-Saito A, Suzuki K, Harada H, Komatsu N, Usuki K, Ichikawa M, Kurokawa M
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Journal Title
Ann Oncol
Volume: 2016 Feb 15
Related Report
Peer Reviewed
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[Journal Article] A C-terminal mutant of CCAAT-enhancer-binding protein α (C/EBPα-C(m)) downregulates Csf1r, a potent accelerator in the progression of acute myeloid leukemia with C/EBPα-C(m).2015
Author(s)
Togami K, Kitaura J, Uchida T, Inoue D, Nishimura K, Kawabata KC, Nagase R, Horikawa S, Izawa K, Fukuyama T, Nakahara F, Oki T, Harada Y, Harada H, Aburatani H, Kitamura T.
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Journal Title
Exp Hematol.
Volume: 43(4)
Issue: 4
Pages: 300-308
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] SETBP1 mutations drive leukemic transformation in ASXL1-mutated MDS.2015
Author(s)
Inoue D, Kitaura J, Matsui H, Hou HA, Chou WC, Nagamachi A, Kawabata KC, Togami K, Nagase R, Horikawa S, Saika M, Micol JB, Hayashi Y, Harada Y, Harada H, Inaba T, Tien HF, Abdel-Wahab O, Kitamura T.
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Journal Title
Leukemia
Volume: 29(4)
Issue: 4
Pages: 847-57
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] XPO1 inhibition targets transcriptional vulnerability of FLT3-ITD+D835 double mutant AML through p53 accumulation and inhibition of oncogenic transcription factors: Lesson learned from CAGE sequencing of primary AML cells.2017
Author(s)
Yamatani K, Tabe Y, Sekihara K, Yang H, Saitoh K, Zhang W, Ikeo K, Kinjo S, Mogushi K, Hosoya M, Hayashizaki Y, Yamanaka Y, Harada H, Miida T, Konopleva M, Andreeff M.
Organizer
59th ASH Annual Meeting and Exposition
Related Report
Int'l Joint Research
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[Presentation] Human Germline HLTF E259K Mutation Identified in Familial MDS Patients Accumulates DNA Damage through Impaired PCNA Polyubiquitination.2017
Author(s)
Takaoka K, Kawazu M, Koya J, Yoshimi A, Masamoto Y, Maki H, Toya T, Kobayashi T, Nannya Y, Arai S, Ueno H, Suzuki K, Harada H, Manabe A, Hayashi Y, Mano H, Kurokawa M.
Organizer
59th ASH Annual Meeting and Exposition
Related Report
Int'l Joint Research
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[Presentation] Novel fatty acid oxidation inhibitor Avocatinb induces AMPK-dependent apoptosis of AML cells co-cultured with BM-adipocytes.2016
Author(s)
Tabe Y, Sekihara K, Saitoh K, Monma N, Ikeo K, Kaczkowski B, Zhang W, Yamanaka Y, Miida T, Shah N, Harada H, Hayashizaki Y, Konopleva M, Andreeff M.
Organizer
58th ASH Annual Meeting and Exposition
Place of Presentation
SanDiego, CA (USA)
Year and Date
2016-12-03
Related Report
Int'l Joint Research
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[Presentation] Nationwide epidemiological surver of familial myelodysplastic syndromes/acute myeloid leukemia in Japan.2016
Author(s)
Takaoka K, Yoshimi A, Koya J, Toya T, Kobayashi T, Nannya Y, Ueno H, Suzuki K, Harada H, Manabe A, Hayashi Y, Kurokawa M.
Organizer
第78回日本血液学会学術集会
Place of Presentation
パシフィコ横浜（神奈川県横浜市）
Year and Date
2016-10-13
Related Report
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[Presentation] Analysis of Asxl1-MT conditional knock-in mice.2016
Author(s)
Nagase R, Inoue D, Kanai A, Saika M, Fujino T, Kawabata K, Tanaka Y, Fukuyama T, Harada H, Goyama S, Honda H, Kitamura T.
Organizer
第78回日本血液学会学術集会
Place of Presentation
パシフィコ横浜（神奈川県横浜市）
Year and Date
2016-10-13
Related Report
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[Presentation] Expansion of ABCG2 is regulated in EZH2-related MDS and associated with its pathogenesis.2016
Author(s)
Kawabata K, Hayashi Y, Inoue D, Sakurai H, Mizuno H, Kitaura J, Harada Y, Harada H, Goyama S, Aburatani H, Ishii M, Kitamura T.
Organizer
第78回日本血液学会学術集会
Place of Presentation
パシフィコ横浜（神奈川県横浜市）
Year and Date
2016-10-13
Related Report
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[Presentation] 家族性骨髄異形成症候群/急性骨髄性白血病の本邦における疫学2016
Author(s)
Takaoka K, Yoshimi A, Koya J, Kobayashi T, Ueno H, Suzuki K, Harada H, Manabe A, Hayashi Y, Kurokawa M.
Organizer
第14回日本臨床腫瘍学会学術集会
Place of Presentation
神戸国際会議場（兵庫県神戸市）
Year and Date
2016-07-28
Related Report
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[Presentation] HIF-1a Pathway, As a Signal Funnel for Genetic, Epigenetic, and Metabolic Aberrations, Is Sufficient and Essential for MDS Development2015
Author(s)
Hayashi Y, Zhang Y, Yan X, Choi K, Sashida G, Dong Y , Xu Z, Wu L, Chen A, Sun X, Olsson A, Harada H, Shih L-Y, Tse W, Bridges J, Witte DP, Wang Q , Caligiuri MA, Grimes HL, Nimer SD, Xiao Z, Huang G
Organizer
57th ASH Annual Meeting and Exposition
Place of Presentation
San Francisco, CA
Year and Date
2015-12-06
Related Report
Int'l Joint Research
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[Presentation] Nationwide epidemiological survey of familial platelet disorder in Japan2015
Author(s)
Toya T, Yoshimi A, Takaoka K, Nannya Y, Kirito K, Ito E, Nakajima H, Hayashi Y, Takahashi T, Moriya-Saito A, SuzukiK, Harada H, Komatsu N, Usuki K, Ichikawa M, Kurokawa M
Organizer
第77回日本血液学会学術集会
Place of Presentation
金沢
Year and Date
2015-10-16
Related Report
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[Presentation] Investigation of a causal gene of familial myelodysplastic syndromes2015
Author(s)
Takaoka K, Kawazu M, Yoshimi A, Toya T, Kobayashi T, Nannya Y, Ueno H, Suzuk K, Harada H, Manabe A, Hayashi Y, Mano H, Kurokawa M
Organizer
第77回日本血液学会学術集会
Place of Presentation
金沢
Year and Date
2015-10-16
Related Report
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