Molecular studies of IG translocation and PVT1 and DCC gene rearrangements in multiple myeloma
| Project/Area Number |
22591045
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | 多発性骨髄腫 / SKY / FISH / ゲノムアレイ / 遺伝子再構成 |
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| Research Abstract |
To elucidate pathophysiology of multiple myeloma (MM), we performed molecular dissection of the breakpoints at chromosomal 8q24 and 18q21 rearrangements using FISH, SKY, oligonucleotide array , and RT -PCR procedures. PVT1 rearrangements were detected in 7 (13.0%) of 54 MM patients and 5 (45.5 %) of 11 MM cell lines. Two novel chimeric genes were identified, PVT1-NBEA and PVT1-WWOX. The PVT1-NBEA chimera in which PVT1 exon 1 was fused to NBEA exon 2 and the PVT1-WWOX in which PVT1 exon 1 was fused to WWOX exon 9 were associated with the expression of abnormal NBEA and WWOX lacking their N-terminus, respectively.These findings suggest that PVT1 rearrangements may represent a novel molecular paradigm underlying the pathology of 8q24 rearrangement-positive multiple myeloma. On the other hand, our studies focusing on 18q21 identified abnormal DCC transcripts in which DCC exon 2 was fused to part of DCC intron 1 hence lacking exon 1 in 15 cell lines using bubble PCR for cDNA. Putative abnormal DCC protein lacks a part of N-terminus, suggesting that structural abnormalities of DCC play some roles in the development and progression of MM.
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Report
(4 results)
Research Products
(134 results)
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[Journal Article] ADAMTS-13 activity can predict the outcome of disseminated intravascular coagulation in hematologic malignancies treated with recombinant human soluble thrombomodulin2012
Author(s)
Ohshiro M, Kuroda J, Kobayashi Y, Akaogi T, Kawata E, Uoshima N, Kamitsuji Y, Kaneko H, Shimura K, Shimazaki C, Murakami S, Hatsuse M, Okano A, Kobayashi T, Uchiyama H, Matsumoto Y, Horiike S, Taniwaki M
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Journal Title
Am J Hematol
Volume: 87(1)
Pages: 116-119
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[Journal Article] Double-hit Lymphomas Constitute a Highly Aggressive Subgroup in Diffuse Large B-cell Lymphomas in the Era of Rituximab2012
Author(s)
Kobayashi T, Tsutsumi Y, Sakamoto N, Nagoshi H, Yamamoto-Sugitani M, Shimura Y, Mizutani S, Matsumoto Y, Nishida K, Horiike S, Asano N, Nakamura S, Kuroda J, Taniwaki M
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Jpn J Clin Oncol
Volume: 42(11)
Pages: 1035-42
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[Journal Article] Overexpression of the DNA sensor proteins, absent in melanoma 2 and interferon-inducible 16, contributes to tumorigenesis of oral squamous cell carcinoma with p53 inactivation2012
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Kondo Y, Nagai K, Nakahata S, Saito Y, Ichikawa T, Suekane A, Taki T, Iwakawa R, Enari M, Taniwaki M, Yokota J, Sakoda S, Morishita K
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Journal Title
Cancer Sci
Volume: 103(4)
Pages: 782-790
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[Journal Article] Establishment of a novel human myeloid leukemia cell line, AMU-AML1, carrying t(12;22)(p13;q11) without chimeric MN1-TEL and with high expression of MN12012
Author(s)
Gotou M, Hanamura I, Nagoshi H, Wakabayashi M, Sakamoto N, Tsunekawa N, Horio T, Goto M, Mizuno S, Takahashi M, Suganuma K, Yamamoto H, Hiramatsu A, Watarai M, Shikami M, Imamura A, Mihara H, Taki T, Miwa H, Taniwaki M, Nitta M
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Journal Title
Genes Chromosomes Cancer
Volume: 51(1)
Pages: 42-53
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[Journal Article] RSK2Ser227 at N-terminal kinase domain is a potential therapeutic target for multiple myeloma2012
Author(s)
Shimura Y, Kuroda J, Ri M, Nagoshi H, Yamamoto-Sugitani M, Kobayashi T, Kiyota M, Nakayama R, Mizutani S, Chinen Y, Sakamoto N, Matsumoto Y, Horiike S, Shiotsu Y, Iida S, Taniwaki M
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Mol Cancer Ther
Volume: 11
Pages: 2600-9
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[Journal Article] Retrospective analysis of prognostic factors for angioimmunoblastic T -cell lymphoma: a multicenter cooperative study in Japan2012
Author(s)
Tokunaga T, Shimada K, Yamamoto K, Chihara D, Ichihashi T, Oshima R, Tanimoto M, Iwasaki T, Isoda A, Sakai A, Kobayashi H, Kitamura K, Matsue K, Taniwaki M, Tamashima S, Saburi Y, Masunari T, Naoe T, Nakamura S, Kinoshita T
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Journal Title
Blood
Volume: 119(12)
Pages: 2837-2843
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[Journal Article] Frequent PVT1 rearrangement and novel chimeric genes PVT1-NBEA and PVT1-WWOX occur in multiple myeloma with 8q24 abnormality2012
Author(s)
Nagoshi H, Taki T, Hanamura I, Nitta M, Otsuki T, Nishida K, Okuda K, Sakamoto N, Kobayashi S, Yamamoto-Sugitani M, Tsutsumi Y, Kobayashi T, Matsumoto Y, Horiike S, Kuroda J, Taniwaki M
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Journal Title
Cancer Res
Volume: 72(19)
Pages: 4954-62
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[Journal Article] Retrospective analysis of prognostic factors for angioimmunoblastic T-cell lymphoma : a multicenter cooperative study in Japan. Blood2012
Author(s)
Tokunaga T, Shimada K, Yamamoto K, Chihara D, Ichihashi T, Oshima R, Tanimoto M, Iwasaki T, Isoda A, Sakai A, Kobayashi H, Kitamura K, Matsue K, Taniwaki M, Tamashima S, Saburi Y, Masunari T, Naoe T, Nakamura S, Kinoshita T
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Journal Title
Epub ahead of print
Volume: 119
Issue: 12
Pages: 2837-2843
DOI
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[Journal Article] Establishment of a novel human myeloid leukemia cell line, AMU-AML1, carrying t(12 ; 22)(p13 ; q11) without chimeric MN1-TEL and with high expression of MN12012
Author(s)
Gotou M, Hanamura I, Nagoshi H, Wakabayashi M, Sakamoto N, Tsunekawa N, Horio T, Goto M, Mizuno S, Takahashi M, Suganuma K, Yamamoto H, Hiramatsu A, Watarai M, Shikami M, Imamura A, Mihara H, Taki T, Taniwaki M, Nitta M
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Journal Title
Genes Chromosomes Cancer
Volume: 51
Issue: 1
Pages: 42-53
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[Journal Article] Cytotoxic molecule-positive classical Hodgkin's lymphoma: a clinicopathological comparison with cytotoxic molecule-positive peripheral T -cell lymphoma of not otherwise specified type2011
Author(s)
Asano N, Kinoshita T, Tamaru J, Ohshima K, Yoshino T, Niitsu N, Tsukamoto N, Hirabayashi K, Izutsu K, Taniwaki M, Morishima Y, Nakamura S
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Journal Title
Haematologica
Volume: 11
Pages: 1636-1643
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[Journal Article] Eμ/miR-125b transgenic mice develop lethal B-cell malignancies2011
Author(s)
Enomoto Y, Kitaura J, Hatakeyama K, Watanuki J, Akasaka T, Kato N, Shimanuki M, Nishimura K, Takahashi M, Taniwaki M, Haferlach C, Siebert R, Dyer MJS, Asou N, Aburatani H, Nakakuma H, Kitamura T, Sonoki T
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Journal Title
Eμ/miR-125b transgenic mice develop lethal B-cell malignancies
Volume: 25
Pages: 1849-1856
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[Journal Article] Identification of IGHCδ-BACH2 fusion transcripts resulting from cryptic chromosomal rearrangements of 14q32 with 6q15 in aggressive B-cell lymphoma/leukemia2011
Author(s)
Kobayashi S, Taki T, Chinen Y, Tsutsumi Y, Ohshiro M, Kobayashi T, Matsumoto Y, Kuroda J, Horiike S, Nishida K, Taniwaki M
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Journal Title
Genes Chromosomes Cancer
Volume: 50
Pages: 207-216
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[Journal Article] Bcl-2 is a better therapeutic target than c-Myc, but attacking both could be a more effective treatment strategy for B-cell lymphoma with concurrent Bcl-2 and c-Myc overexpression2011
Author(s)
Sasaki N, Kuroda J, Nagoshi H, Yamamoto M, Kobayashi S, Tsutsumi Y, Kobayashi T, Shimura Y, Matsumoto Y, Taki T, Nishida K, Horiike S, Akao Y, Taniwaki M
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Journal Title
Exp Hematol
Volume: 39(8)
Pages: 817-828
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[Journal Article] Galectin-3 (Gal-3) induced by leukemia microenvironment promotes drug resistance and bone marrow lodgment in chronic myelogenous leukemia2011
Author(s)
Yamamoto-Sugitani M, Kuroda J, Ashihara E, Nagoshi H, Kobayashi T, Matsumoto Y, Sasaki N, Shimura Y, Kiyota M, Nakayama R, Akaji K, Taki T, Uoshima N, Kobayashi Y, Horiike S, Maekawa T, Taniwaki M
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Journal Title
Proc Natl Acad Sci U S A
Volume: 108(42)
Pages: 17468-17473
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[Journal Article] Phase II/III study of R-CHOP-21 versus R-CHOP-14 for untreated indolent B-cell non-Hodgkin's lymphoma: JCOG 0203 trial2011
Author(s)
Watanabe T, Tobinai K, Shibata T, Tsukasaki K, Morishima Y, Maseki N, Kinoshita T, Suzuki T, Yamaguchi M, Ando K, Ogura M, Taniwaki M, Uike N, Takeuchi K, Nawano S, Terauchi T, Hotta T
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Journal Title
J Clin Oncol.
Volume: 29
Pages: 3990-3998
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[Journal Article] Expression of master regulators of helper T -cell differentiation in peripheral T -cell lymphoma, not otherwise specified, by immunohistochemical analysis2010
Author(s)
Matsumoto Y, Horiike S, Ohshiro M, Yamamoto M, Sasaki N, Tsutsumi Y, Kobayashi T, Shimizu D, Uchiyama H, Kuroda J, Nomura K, Shimazaki C, Taniwaki M
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Journal Title
Am J Clin Pathol
Volume: 133(2)
Pages: 281-290
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[Journal Article] Targeting activating transcription factor 3 by Galectin-9 induces apoptosis and overcomes various types of treatment resistance in chronic myelogenous leukemia2010
Author(s)
Kuroda J, Yamamoto M, Nagoshi H, Kobayashi T, Sasaki N, Shimura Y, Horiike S, Kimura S, Yamauchi A, Hirashima M, Taniwaki M
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Journal Title
Mol Cancer Res
Volume: 8
Pages: 994-1001
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[Journal Article] Galectin-9 exhibits anti-myeloma activity through JNK and p38 MAP kinase pathways2010
Author(s)
Kobayashi T, Kuroda J, Ashihara E, Oomizu S, Terui Y, Taniyama A, Adachi S, Takagi T, Yamamoto M, Sasaki N, Horiike S, Hatake K, Yamauchi A, Hirashima M, Taniwaki M
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Journal Title
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Volume: 24
Pages: 843-850
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[Presentation] RSK2Ser227is a therapeutic target of myeloma cells regardless of upstream signalings2012
Author(s)
Shimura Y, Kuroda J, Nagoshi H, M Yamamoto-Sugitani M, Kobayashi T, Kiyota M, Nakayama R, Mizutani S, Chinen Y, Sakamoto N, Matsumoto Y, Horiike S, Ri M, Shiotsu Y, Iida S, Taki T, Taniwaki M
Organizer
54th The American Society of Hematology Annual Meeting and Exposition
Place of Presentation
Atlanta. USA
Year and Date
2012-12-09
Related Report
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[Presentation] Identification of the novel chimeric gene, PVT1-WWOX, in multiple myeloma with 8q24 abnormality2012
Author(s)
Nagoshi H, Taki T, Nishida K, Kuroda J, Chinen Y, Kobayashi S*, Yokokawa Y, Yamamoto-Sugitani M, Kobayashi T, Matsumoto Y, Horiike S, Taniwaki M
Organizer
54th The American Society of Hematology Annual Meeting and Exposition
Place of Presentation
Atlanta. USA
Year and Date
2012-12-08
Related Report
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[Presentation] Frequent Involvement of PVT1 in Multiple Myeloma Carrying 8q24 Rearrangement and Identification of Novel PVT1-NBEAChimeric Gene2011
Author(s)
Nagoshi H, Taki T, Hanamura I, Nitta M, Otsuki T, Nishida K, Okuda K, Sakamoto N, Kobayashi S, Yamamoto M, Tsutsumi Y, Kobayashi T, Matsumoto Y, Horiike S, Kuroda J, Taniwaki M
Organizer
53th ASH Annual Meeting
Place of Presentation
San Diego. USA
Year and Date
2011-12-12
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[Presentation] Leukemia Microenvironment-Specific Galectin-3 Expression of Leukemic Cells Promotes Malignant Niche Formation and Bone Marrow Lodgment of leukemic Cells in Chronic Myelogenous Leukemia2011
Author(s)
Kuroda J, Yamamoto M, Ashihara E, Nagoshi H, Kobayashi T, Matsumoto Y, Sasaki N, Shimura Y, Kiyota M, Nakayama R, Horiike S, Maekawa T, Taniwaki M
Organizer
53th ASH Annual Meeting
Place of Presentation
San Diego. USA
Year and Date
2011-12-10
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[Presentation] Frequent rearrangements of PVT1 and a novel PVT1-NBEA chimeric gene in multiple myeloma2011
Author(s)
Nagoshi H, Taki T, Hanamura I, Nishida K, Kuroda J, Okuda K, Kobayashi S, Yamamoto M, Tsutsumi Y, Kobayashi T, Matsumoto Y, Horiike S, Ootsuki T, Nitta M, Taniwaki M
Organizer
第73回日本血液学会学術集会
Place of Presentation
名古屋
Related Report
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[Presentation] 8q24 異常を伴う MM における PVT1の関与および新規キメラ遺伝子PVT1-NBEA の同定2011
Author(s)
名越久朗,滝 智彦,花村一朗,仁田正和,大槻剛己,西田一弘,奥田恵子,小林 覚,山本未央,〓 康彦,古林 勉,松本洋典,堀池重夫,黒田純也,谷脇雅史
Organizer
第70回日本癌学術総会
Place of Presentation
名古屋
Related Report
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[Presentation] Identification and Functional Significance of Novel Type of Structurally Aberrant Transcripts of DCC in B-Cell Malignancies2010
Author(s)
Nagoshi H, Taki T, Kuroda J, Nishida K, Gotoh M, Okuda K, Kobayashi S, Yamamoto M, Tsutsumi Y, Kobayashi T, Matsumoto Y, Horiike S, Otsuki T, Taniwaki M
Organizer
52th ASH Annual Meeting
Place of Presentation
Orlando, USA
Year and Date
2010-12-06
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[Presentation] Expression of altered DCC gene in multiple myeloma and non-Hogdgikin's lymphoma2010
Author(s)
Nagoshi H, Taki T, Kuroda J, Nishida K, Gotoh M, Okuda K, Kobayashi S, Yamamoto M, Tsutsumi Y, Kobayashi T, Matsumoto Y, Horiike S, Otsuki T, Taniwaki M
Organizer
第72回日本血液学会学術集会
Place of Presentation
横浜
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