The molecular mechanism that ATRA induces granulocytic differentiation in leukemic cells through the protein acetylation
Project/Area Number |
26893264
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Research Category |
Grant-in-Aid for Research Activity Start-up
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Allocation Type | Single-year Grants |
Research Field |
Hematology
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Research Institution | Juntendo University |
Principal Investigator |
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Project Period (FY) |
2014-08-29 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | PCAF / 急性前骨髄球性白血病(APL) / 全トランスレチノイン酸(ATRA) / 分化誘導療法 / ヒストンアセチル基転移酵素 / 蛋白質アセチル化 / 急性前骨髄球性白血病 / ATRA / 好中球分化 / 全トランスレチノイン酸 / 分化誘導 |
Outline of Final Research Achievements |
All-trans retinoic acid (ATRA) induces granulocytic differentiation in acute promyelocytic leukemia (APL) cells, however, its detailed molecular mechanism remains unclear. Here, we showed that the overexpression of a histone acetyltransferase PCAF induced the expression of the granulocytic differentiation marker at the mRNA level, suggesting that PCAF is essential for APL cell differentiation. In addition, we found that ATRA acetylated the PCAF substrates while ATRA induced granulocytic differentiation in leukemic cells. Furthermore, PCAF regulated the downstream target gene expression of ATRA. These observations suggested that ATRA induced granulocytic differentiation in APL cells through the PCAF-induced protein acetylation and the PCAF-regulated downstream target gene expression.
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Report
(3 results)
Research Products
(18 results)
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[Journal Article] Activation of the thrombopoietin receptor by mutant calreticulin in CALR-mutant myeloproliferative neoplasms.2016
Author(s)
Araki M, Yang Y, Masubuchi N, Hironaka Y, Takei H, Morishita S, Mizukami Y, Kan S, Shirane S, Edahiro Y, Sunami Y, Ohsaka A, Komatsu N
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Journal Title
Blood
Volume: 127
Issue: 10
Pages: 1307-16
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Consequences of the JAK2V617F allele burden for the prediction of transformation into myelofibrosis from polycythemia vera and essential thrombocythemia.2015
Author(s)
Shirane S, Araki M, Morishita S, Edahiro Y, Sunami Y, Hironaka Y, Noguchi M, Koike M, Sato E, Ohsaka A, Komatsu N.
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Journal Title
Int J Hematol
Volume: 101
Issue: 2
Pages: 148-53
DOI
Related Report
Peer Reviewed
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[Journal Article] JAK2, CALR, and MPL mutation status in Japanese myeloproliferative neoplasms patients2015
Author(s)
Shirane S, Araki M, Morishita S, Edahiro Y, Sunami Y, Hironaka Y, Noguchi M, Koike M, Ohsaka A, and Komatsu N
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Journal Title
Haematologica
Volume: 100
Issue: 2
Pages: e46-e48
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Detection of MPLW515L/K mutations and determination of allele frequencies with a single-tube PCR assay2014
Author(s)
Takei H, Morishita S, Araki M, Edahiro Y, Sunami Y, Hironaka Y, Noda N, Sekiguchi Y, Tsuneda S, Ohsaka A, and Komatsu N
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Journal Title
PLoS ONE
Volume: 9
Issue: 8
Pages: e104958-e104958
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Rituximab plus a CHOP-like regimen, central nervous system prophylaxis, and contralateral testicular irradiation for localized primary testicular diffuse large B-cell lymphoma lead to prolonged progression-free survival.2014
Author(s)
Ichikawa K, Noguchi M, Koike M, Aritaka N, Sekiguchi Y, Sunami Y, Tsutsui M, Hosone M, Hirano T, Gotoh A, Komatsu N
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Journal Title
Int J Hematol
Volume: 100
Issue: 4
Pages: 370-8
DOI
Related Report
Peer Reviewed
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[Journal Article] JAK2V617F mutation status and allele burden in classical Ph-negative myeloproliferative neoplasms in Japan2014
Author(s)
EdahiroY, Morishita S, Takahashi K, Hironaka Y, Yahata Y, Sunami Y, Shirane S, Tsutsui M, Noguchi M, Koike M, Imai K, Noda N, Sekiguchi Y, Tsuneda S, Ohsaka A, Araki M, Komatsu N
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Journal Title
Int J Hematol
Volume: 99(5)
Issue: 5
Pages: 625-634
DOI
Related Report
Peer Reviewed
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[Presentation] Establishment of a novel assay for MPLW515/K detection and allele burden measurement (Japanese).2014
Author(s)
Takei H, morishita S, Araki M, Edahiro Y, Sunami Y, Hironaka Y, Noda N, Sekiguchi Y, Tsuneda S, Ohsaka A, Komatsu N.
Organizer
76th Annual Meeting of the Japanese Society of Hematology
Place of Presentation
Osaka, Japan
Year and Date
2014-10-31
Related Report
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[Presentation] MPL mutation analysis of Ph-negative myeloproliferative neoplasms in Japan.2014
Author(s)
Edahiro Y, Shirane S, Takei H, morishita S, Sunami Y, Hironaka Y, Tsuneda S, Ohsaka A, Araki M, Komatsu N.
Organizer
76th Annual Meeting of the Japanese Society of Hematology
Place of Presentation
Osaka, Japan
Year and Date
2014-10-31
Related Report
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