Elucidation of molecular mechanisms of drug-resistant leukemia through micro RNA analysis : applications to laboratory diagnostics

• Project/Area Number: 21590640
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Tokai University
• Principal Investigator: MIYACHI Hayato 東海大学, 医学部, 教授 (20174196)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 白血病 / 抗癌剤 / 耐性 / マイクロRNA / 抗がん剤 / FLT-3 / Ara-C / 抗癌剤耐 / FLT-3-I / 白血病細胞 / 抗癌剤耐性 / FLT3-ITD

Research Abstract

Expression of numerous genes is altered in drug-resistant tumor cells. MicroRNA is known as a regulating factor in the gene expression. The aim of this study was to clarify roles of micro RNA expression in drug-resistant leukemia cells, and its possible application in the diagnosis of resistance. When leukemia cells were transfected with FLT3-ITD, a major poor risk factor, specific resistance to ara-C was found. Altered pattern of micro RNA was demonstrated when analyzed by DNA microarray. This experimental system can be used as a model for diagnosis of drug resistance.

Research Products

• [Journal Article] Successful Treatment of Childhood Hypocellular Acute Myeloid Leukemia (2012)
  • Author(s): Yamamoto M, Hori T, Hatakeyama N, Igarashi K, Iesato K, Nakanishi K, Noguchi H, Miyachi H, Ito M, Tsutsumi H, Suzuki N
  • Journal Title: J Pediatr Hematol Oncol Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Clinical and pathological features of B-cell non-Hodgkin lymphomas lacking the surface expression of immunoglobulin light chain (2012)
  • Author(s): Matsushita H, Nakamura N, Tanaka Y, Ohgiya D, Tanaka Y, Damdinsuren A, Asai S, Yabe M, Kawada H, Ogawa Y, Ando K, Miyachi H
  • Journal Title: Clin Chem Lab Med Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] The sonographic appearance of the submandibular glands in patients with IgG4-related disease (2012)
  • Author(s): Asai S, Okami K, Nakamura N, Shiraishi S, Yamashita T, Anar D, Matsushita H, Miyachi H
  • Journal Title: J Ultrasound Med Volume: 31 Pages: 489-493
  • Peer Reviewed
• [Journal Article] Clinical and pathological features of B-cell non-Hodgkin lymphomas lacking the surface expression of immunoglobulin light chain (2012)
  • Author(s): Matsushita H, el
  • Journal Title: Clin Chem Lab Med
  • Peer Reviewed
• [Journal Article] Infantile acute promyelocytic leukemia without an RARα rearrangement (2011)
  • Author(s): Hori T, Suzuki N, Hatakeyama N, Yamamoto M, Inazawa N, Miyachi H, Taki T, Tsutsumi H
  • Journal Title: Pediatrics International Volume: 53 Pages: 1070-1073
  • Peer Reviewed
• [Journal Article] Triage of lymphoid malignancies in the peripheral blood using the Extended Immunofluorescent Application of the CELL-DYN Sapphire automated hematology analyzer (2011)
  • Author(s): Matsushita H, Gondo K, Tanaka Y, Miyachi H
  • Journal Title: Clin Chem Lab Med Volume: 49 Pages: 933-935
  • Peer Reviewed
• [Journal Article] Establishment of a xenograft model of human myelodysplastic syndromes (2011)
  • Author(s): Muguruma Y, Matsushita H, Yahata T, Shizu Y, Tanaka Y, Miyachi H, Ogawa Y, Kawada H, Ito M, Ando K
  • Journal Title: Haematologica Volume: 96 Pages: 543-551
  • Peer Reviewed
• [Journal Article] Infantile acute promyelocytic leukemia without an RARα rearrangement (2011)
  • Author(s): Hori T, et al
  • Journal Title: Pediatrics International Volume: 53 Pages: 1070-1096
  • Peer Reviewed
• [Journal Article] Companion Diagnostics:臨床応用の意義と仮題 (2011)
  • Author(s): 宮地勇人
  • Journal Title: 臨床病理 Volume: 59 Pages: 602-608
• [Journal Article] 白血病における抗がん剤耐性の分子機構 (2011)
  • Author(s): 宮地勇人, 他
  • Journal Title: 血液内科 Volume: 63 Pages: 493-497
• [Journal Article] Triage of lymphoid malignancies in the peripheral blood using the Extended immunofluorescent application of the CELL-DYN Sapphire automated hematology analyzer. (2011)
  • Author(s): Matsushita H, et al
  • Journal Title: Clin Chem Lab Med Volume: 49 Pages: 552-554
  • Peer Reviewed
• [Journal Article] Establishment of a xenograft model of human myelodysplastic syndrome (2011)
  • Author(s): Muguruma Y, et al.
  • Journal Title: Haematologica Volume: 96(In press)
  • Peer Reviewed
• [Journal Article] Differential coexpression of Mex efflux pumps in a clinical strain of metallo-β-lactamase-producing pseudomonas aeruginosa during the stepwise evolution of resistance to aminoglycosides. (2011)
  • Author(s): Asai S., et al.
  • Journal Title: Inf Dis Clin Pract Volume: 19 Pages: 38-42
  • Peer Reviewed
• [Journal Article] The tortoiseshell pattern in one or both sides of the submandibular glands in mucosa-associated lymphoid tissue lymphoma is related to chromosomal aberrations and the disease extent (2010)
  • Author(s): Asai S, Okami, K, Nakamura, N, Ogawa Y, Ohta Y, Ogase Y, Jin G, Matsushita, H, Miyachi H
  • Journal Title: J Ultrasound Med Volume: 29 Pages: 111-115
  • Peer Reviewed
• [Journal Article] A novel aberrant form of e13a2 BCR-ABL1 transcript in chronic myelogenous leukemia undetectable with the standardized real-time quantitative polymerase chain reaction from the Europe Against Cancer Program (2009)
  • Author(s): Matsushita, H, Yamamoto M, Tsuboi K, Masukawa A, Arakawa S, Asai S. Ogawa Y, Ando K, Miyachi H
  • Journal Title: Clin Chem Lab Med Volume: 47 Pages: 885-887
  • Peer Reviewed
• [Journal Article] FLT3-ITD induces ara-C resistance in myeloid leukemic cells through the repression of the ENT1 expression (2009)
  • Author(s): Jin G, Matsushita H, Asai S, Tsukamoto H, Ono R, Nosaka T, Yahata T, Takahashi S, Miyachi H
  • Journal Title: Biochem Biophys Res Comm Volume: 390 Pages: 1001-1006
  • Peer Reviewed
• [Journal Article] Persistence of derivative chromosome 22 after achieving a major molecular response in chronic myeloid leukemia with a cryptic BCR-ABL1 fusion gene (2009)
  • Author(s): Matsushita H, Masukawa A, Arakawa S, Ogawa Y, Asai S, Yabe M, Ando K, Miyachi H
  • Journal Title: Intern J Hematol Volume: 90 Pages: 623-626
  • NAID: 10026110078
  • Peer Reviewed
• [Journal Article] FLT3-ITD induces ara-C resistance in myeloid leukemic cells through the repression of ENT1 expression (2009)
  • Author(s): Jin Q, et al
  • Journal Title: Biochem Biophys Res Comm 390 Pages: 1001-1006
  • Peer Reviewed
• [Journal Article] A novel abberant form of e13a2 BCR-ABL1 transcript in chronic myelogenous leukemia undetectable with standardized real-time quantitative polymerase (2009)
  • Author(s): Matsushita H, et al
  • Journal Title: Clin Chem Lab Med 47 Pages: 885-887
  • Peer Reviewed
• [Journal Article] Persistence of derivetive chromosome 22 after achieving a major molecular response in chronic myeloid leukemia with a cryptic BCR-ABL1 fusion gene. (2009)
  • Author(s): Matsushita H, et al.
  • Journal Title: Int J Hematol 90 Pages: 623-626
  • Peer Reviewed
• [Presentation] Global Standardization and quality services of molecular-genetic testing (2011)
  • Author(s): Miyachi H
  • Organizer: ASCP Annual Meeting/WASPaLM XXVI World Congress
  • Place of Presentation: Las Vegas, USA
  • Year and Date: 2011-10-20
• [Presentation] CD34+/CD38+cells from human cord blood initiate APL by induction of PML-RARA (2011)
  • Author(s): Matsushita H, Yahata T, Nakamura Y, Sheng Y, Muguruma Y, Matsuzawa H, Uno T, Takanashi T, Satou T, Tanaka M, Hayashi H, Miyachi H, Ando K
  • Organizer: The 73^<rd> annual meeting of the Japanese Society of Hematology
  • Place of Presentation: 名古屋国際会議場(名古屋)
  • Year and Date: 2011-10-16
• [Presentation] Various chromosomal aberrations arising after RIC-CBT in childhood hypocellular AML (2011)
  • Author(s): Yamamoto M, Igarashi K, Hatakeyama N, Suzuki N, Tsutsumi H, Noguchi H, Nakanishi K, Ito M, Miyachi H, Oda T
  • Organizer: The 73^<rd> annual meeting of the Japanese Society of Hematology
  • Place of Presentation: 名古屋国際会議場(名古屋)
  • Year and Date: 2011-10-15