Leukemogenicity of the RCSD1-ABL1 gene

• Project/Area Number: 26461434
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Nippon Medical School
• Principal Investigator: Inokuchi Koiti 日本医科大学, 大学院医学研究科, 大学院教授 (10203267)
• Co-Investigator(Kenkyū-buntansha): 玉井 勇人 日本医科大学, 医学部, 講師 (40465349)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: RCSD1 / ABL1 / ALL / Ba /F3 / TKI / Tyk2 / B-ALL / RCSD1-ABL1 / ＡＬＬ / ＭＯＣＫ / 遺伝子導入 / 白血病 / BaF3 / TK

Outline of Final Research Achievements

Two RCSD1-ABL1 ｃDNA were cloned from a cells of RCSD1-ABL1-positive acute leukemia.One is cDNA consisted of exon 3 of RCSD1/ exon 4 of ABL1 (R3A4), another is consisted of exon 2 of RCSD1/ exon 4 of ABL1 (R2A4). R3A4 and R2A4 were expressed in Ba/F3 cells using retrovectors. Using phosphorylation antibody array detected the increased phosphorylation of Tyk2 in R3A4-Ba/F3 cells. Wester blotting analysis confirmed the increased phosphorylation of Tyk2, although no increased phosphorylation of Tyk2 in R2A4-Ba/F3 cells. Tyrosine kinase inhibitor assays also showed the sensitivity of R3A4-Ba/F3 cells to the TKIS imatinib, dasatinib, and JAK2 inhibitor I, which is a pan family including Tyk2 inhibitor. R3A4-Ba/F3 cells showed sensitivity only to JAK-inhibitor I. These findings suggest that the kinase-activating pathways and sensitivities to TKIs vary between fusion sites of RCSD1-ABL1 in leukemogenesis.

Research Products

• [Journal Article] The kinase-activating pathways and sensitivities to TKIs vary between fusion sites of RCSD1-ABL1 in Ph-like acute lymphoblastic leukemia. (2016)
  • Author(s): 1.Tamai H, Yamaguchi H, Miyake K, Takatori M, Kitano T, Dan K, Inokuchi K.
  • Journal Title: International Journal of Recent Scientific Research Volume: 7 Pages: 9729-9733
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The Kinase-Activating Pathways and Sensitivities to TKIs Vary between Fusion sites of RCSD1–ABL1 in Ph-like Acute Lymphoblastic Leukemia (2016)
  • Author(s): Hayato Tamai, Hiroki Yamaguchi, Koichi Miyake, Miyuki Takatori,Tomoaki Kitano, Kazuo Dan and Koiti Inokuchi
  • Journal Title: International Journal of Recent Scientific Research Volume: 7 Pages: 10-20
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Complex molecular genetic abnormalities involving three or more genetic mutations are important prognostic factors for acute myeloid leukemia. (2016)
  • Author(s): Wakita S, Yamaguchi H, Ueki T, Usuki K, Kurosawa S, Kobayashi Y, Kawata E, Tajika K, Gomi S, Koizumi M, Fujiwara Y, Yui S, Fukunaga K, Ryotokuji T, Hirakawa T, Arai K, Kitano T, Kosaka F, Tamai H, Nakayama K, Fukuda T, Inokuchi K
  • Journal Title: Leukemia Volume: 60 Issue: 22 Pages: 545-554
  • DOI: 10.1182/blood-2015-05-646240
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Shorter halving time of BCR-ABL1 transcripts is a novel predictor for achievement of molecular responses in newly diagnosed chronic-phase chronic myeloid leukemia treated with dasatinib: Results of the D-first study of Kanto CML study group (2015)
  • Author(s): 1.Iriyama N, Fujisawa S, Yoshida C, Wakita H, Chiba S, Okamoto S, Kawakami K, Takezako N, Kumagai T, Inokuchi K, Ohyashiki K, Taguchi J, Yano S, Igarashi T, Kouzai Y, Morita S, Sakamoto J, Sakamaki H
  • Journal Title: Am J Hematol Volume: ９０ Issue: 4 Pages: 282-287
  • DOI: 10.1002/ajh.23923
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Efficacy of molecular response at 1 or 3 months after the initiation of dasatinib treatment can predict an improved response to dasatinib in imatinib-resistant or imatinib-intolerant Japanese patients with chronic myelogenous leukemia during the chronic phase. (2014)
  • Author(s): 2.Inokuchi K, Kumagai T, Matsuki E, Ohashi K, Shinagawa A, Hatta Y, Takeuchi J, Yoshida C, Wakita H, Kozai Y, Shirasugi Y, Fujisawa S, Iwase O, Yano S, Okamoto S, Oba K, Sakamoto J, Sakamaki H
  • Journal Title: J Clin Exp Hematop Volume: ５４ Pages: 197-204
  • NAID: 130004705266
  • Peer Reviewed
• [Journal Article] nhibition of S100A6 induces graft versus leukemia effects in MLL/AF4-positive ALL in human PBMC-SCID mice. (2014)
  • Author(s): Tamai.H, Miyake K, Yamaguchi H, Shimada T, Dan K, Inokuchi K.
  • Journal Title: Bone Marrow Transplantation Volume: 49(5) Issue: 5 Pages: 699-703
  • DOI: 10.1038/bmt.2014.18
  • Peer Reviewed / Open Access
• [Presentation] The examination of RCSD1-ABL1- leukemogenicity (2015)
  • Author(s): Tamai H,Miyake K, Yamaguchi H, Dan K, Inokuchi K.
  • Organizer: The 76th Annual Meeting of the Japanese Society of Hematology
  • Place of Presentation: Nagoya, Japan
  • Year and Date: 2015-10-31