Functional analysis of candidate leukemia suppressor genes located on the long arm of chromosome 7

• Project/Area Number: 22790912
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Hematology
• Research Institution: Hiroshima University
• Principal Investigator: MATSUI Hirotaka 広島大学, 原爆放射線医科学研究所, 准教授 (60379849)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: -7/ 7q-MDS / 初期エンドソーム / Titan (Samd9L) / AML/MDS / 7q欠損 / 急性骨髄性白血病 / 骨髄異形成症候群 / エンドサイトーシス

Research Abstract

We analyzed molecular functions of Samd9/ Samd9L, genes isolated as candidate responsible genes for MDS/ AML carrying monosomy 7/ 7q-. Samd9L protein was found to be partially localized at early endosomal fraction. In Samd9L-downregulated cells, the inhibition of fusion of early endosomes, which resulted in the accumulation of activated cytokine receptors in early endosomal fraction, caused prolongation of cytokine signals. Collectively, it became relevant that Samd9L negatively regulates cytokine signals through the promotion of the degradation of cytokine receptors by facilitating the fusion of early endosomes.

Research Products

• [Journal Article] The dynactin complex maintains the integrity of metaphasic centrosomes to ensure transition to anaphase (2011)
  • Author(s): Ozaki Y, Matsui H, Nagamachi A, Asou H, Aki D, Inaba T
  • Journal Title: Journal of Biological Chemistry Volume: 286(7) Pages: 5589-5598
  • Peer Reviewed
• [Journal Article] Rapid emergence of telaprevir resistant hepatitis Cvirus strain from wildtype clone in vivo (2011)
  • Author(s): Hiraga N, Imamura M, Abe H, Hayes CN, Kono T, Onishi M, Tsuge M, Takahashi S, Ochi H, Iwao E, Kamiya N, Yamada I, Tateno C, Yoshizato K, Matsui H, Kanai A, Inaba T, Tanaka S, Chayama K
  • Journal Title: Hepatology Volume: 54(3) Pages: 781-788
  • Peer Reviewed
• [Journal Article] The Samd9L gene : transcriptional regulation andtissue-specific expression in mousedevelopment (2011)
  • Author(s): Jiang Q, Quaynor B, Sun A, Li Q, Matsui H, Honda H, Inaba T, Sprecher E, Uitto J
  • Journal Title: J Invest Dermatol Volume: 131(7) Pages: 1428-1434
  • Peer Reviewed
• [Journal Article] Rapidemergence of telaprevir resistanthepatitis C virus strain from wildtypeclone in vivo (2011)
  • Author(s): Hiraga N, Imamura M, Abe H, Hayes CN, Kono T, Onishi M, Tsuge M, TakahashiS, Ochi H, Iwao E, Kamiya N, Yamada I, Tateno C, Yoshizato K, Matsui H, KanaiA, Inaba T, Tanaka S, Chayama K
  • Journal Title: Hepatology Volume: 54 Issue: 3 Pages: 781-788
  • DOI: 10.1002/hep.24460
  • Peer Reviewed
• [Journal Article] The Samd9L gene : transcriptional regulation and tissue-specific expression in mouse development (2011)
  • Author(s): Jiang Q., et al
  • Journal Title: J Invest Dermatol Volume: 131 Issue: 7 Pages: 1428-1434
  • DOI: 10.1038/jid.2011.61
  • Peer Reviewed
• [Journal Article] The dynactin complex maintains the integrity of metaphasic centrosomes to ensure transition to anaphase. (2011)
  • Author(s): Ozaki Y, et al.
  • Journal Title: Journal of Biological Chemistry Volume: 286(7) Pages: 5589-5598
  • Peer Reviewed
• [Journal Article] Aberrantinduction of LMO2 by the E2A-HLF chimeric transcription factor and itsimplication in leukemogenesis of B-precursor ALL with t(17 ; 19) (2010)
  • Author(s): Hirose K, Inukai T, Kikuchi J, Furukawa Y, Ikawa T, Kawamoto H, Oram SH, GottgensB, Kiyokawa N, Miyagawa Y, Okita H, Akahane K, Zhang X, Kuroda I, Honna H, Kagami K, Goi K, Kurosawa H, Look AT, Matsui H, Inaba T, Sugita K
  • Journal Title: Blood Volume: 116(6) Pages: 962-970
  • Peer Reviewed
• [Journal Article] Aberrant induction of LMO2 by the E2A-HLF chimeric transcription factor and its implication in leukemogenesis of B-precursor ALL with t(17;19). (2010)
  • Author(s): Hirose K, et al.
  • Journal Title: Blood Volume: 116(6) Pages: 962-970
  • Peer Reviewed
• [Presentation] Titan(Samd9L), a candidate-7/ 7q-responsible gene product, downregulates cytokine signals byfacilitating formation of earlyendosome (2011)
  • Author(s): Matsui H
  • Organizer: 第53回米国血液学会年次総会
  • Place of Presentation: サンディエゴ(米国)
  • Year and Date: 2011-12-12
• [Presentation] Titan (Samd9L), a candidate-7/7q-responsible gene product, downregulates cytokine signals by facilitating formation of early endosome (2011)
  • Author(s): 松井啓隆
  • Organizer: 第53回米国血液学会年次総会
  • Place of Presentation: サンディエゴ(米国)
  • Year and Date: 2011-12-12
• [Presentation] Analysis of epigenetic alterationsby 5-Azacitidine that induces erythroiddifferentiation using a next generationsequencer (2011)
  • Author(s): Matsui H
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋市
  • Year and Date: 2011-10-15
• [Presentation] Analysis of epigenetic alterations by 5-Azacitidine that induces erythroid differentiation using a next generation sequencer (2011)
  • Author(s): 松井啓隆
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋市
  • Year and Date: 2011-10-15
• [Presentation] Analysis of epigenetic changes by5-Azacitidine that induces erythroiddifferentiation using a next generationsequencer (2011)
  • Author(s): Matsui H
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋市
  • Year and Date: 2011-10-05
• [Presentation] Analysis of epigenetic changes by 5-Azacitidine that induces erythroid differentiation using a next generation sequencer (2011)
  • Author(s): 松井啓隆
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋市
  • Year and Date: 2011-10-05
• [Presentation] Development of myeloidneoplasia in mice deficient for endosomefusion facilitator(eff)-2 gene that mimichuman myeloid malignancies carryingmonosomy 7 (2011)
  • Author(s): Matsui H
  • Organizer: 第70回日本癌学会学術総会(招待講演)
  • Place of Presentation: 名古屋市
  • Year and Date: 2011-10-03
• [Presentation] Development of myeloid neoplasia in mice deficient for endosome fusion facilitator (eff)-2 gene that mimic human myeloid malignancies carrying monosomy 7 (2011)
  • Author(s): 松井啓隆
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋市(招待講演)
  • Year and Date: 2011-10-03
• [Presentation] Isolation and characterization of 7q-responsible genes that encode endosomalproteins (2011)
  • Author(s): Matsui H
  • Organizer: 第2回日本血液学会国際シンポジウム(招待講演)
  • Place of Presentation: 長崎市
  • Year and Date: 2011-04-23
• [Presentation] Isolation and characterization of 7q-responsible genes that encode endosomal proteins (2011)
  • Author(s): 松井啓隆
  • Organizer: 第2回日本血液学会国際シンポジウム
  • Place of Presentation: 長崎市(招待講演)
  • Year and Date: 2011-04-23
• [Presentation] Titan(Samd9L), a candidate-7/ 7q-responsible gene product, downregulates cytokine signals by facilitating formation of early endosomes (2010)
  • Author(s): Matsui H
  • Organizer: 第52回米国血液学会総会
  • Place of Presentation: オーランド(米国)
  • Year and Date: 2010-12-06
• [Presentation] Titan (Samd9L), a candidate -7/7q-responsible gene product, downregulates cytokine signals by facilitating formation of early endosomes. (2010)
  • Author(s): 松井啓隆
  • Organizer: 第52回米国血液学会総会
  • Place of Presentation: 米国、オーランド
  • Year and Date: 2010-12-06
• [Presentation] 番染色体長腕欠損による白血病発症メカニズム:責任遺伝子の単離と機能解析 (2010)
  • Author(s): 松井啓隆
  • Organizer: 第53回放射線影響学会大会(招待講演)
  • Place of Presentation: 京都市
  • Year and Date: 2010-10-20
• [Presentation] 7番染色体長腕欠損による白血病発症メカニズム:責任遺伝子の単離と機能解析 (2010)
  • Author(s): 松井啓隆
  • Organizer: 第53回放射線影響学会大会
  • Place of Presentation: 京都市(招待講演)
  • Year and Date: 2010-10-20
• [Presentation] Titan(Samd9L), a candidate 7qresponsiblegene product, promotesdegradation of cytokine receptors (2010)
  • Author(s): Matsui H
  • Organizer: 第72回日本血液学会総会
  • Place of Presentation: 横浜市
  • Year and Date: 2010-09-24
• [Presentation] Titan (Samd9L), a candidate 7q-responsible gene product, promotes degradation of cytokine receptors. (2010)
  • Author(s): 松井啓隆
  • Organizer: 第72回日本血液学会総会
  • Place of Presentation: 横浜市
  • Year and Date: 2010-09-24
• [Presentation] Titan(Samd9L), a candidate-7/ 7q-responsible gene product, promotesdegradation of cytokine receptors (2010)
  • Author(s): Matsui H
  • Organizer: 第69回日本癌学会総会
  • Place of Presentation: 大阪市
  • Year and Date: 2010-09-23
• [Presentation] Titan (Samd9L), a candidate -7/7q-responsible gene product, promotes degradation of cytokine receptors. (2010)
  • Author(s): 松井啓隆
  • Organizer: 第69回日本癌学会総会
  • Place of Presentation: 大阪市
  • Year and Date: 2010-09-23