Elucidation of mechanisms of myelodysplastic syndrome progression by RNAi screening.

• Project/Area Number: 25670445
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Hematology
• Research Institution: The University of Tokyo
• Principal Investigator: KUROKAWA Mineo 東京大学, 医学部附属病院, 教授 (80312320)
• Co-Investigator(Renkei-kenkyūsha): KATAOKA Keisuke 東京大学, 医学部附属病院, 特任助教 (90631383)
• Project Period (FY): 2013-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• Keywords: 骨髄異形成症候群 / 治療抵抗性 / RNAiスクリーニング / 網羅的ゲノム解析

Research Abstract

The aim of this study is to elucidate the mechanism of resistance to treatment in myelodysplastic syndrome (MDS) patients by using RNA-interference technologies. We employed the small-hairpin RNA plasmid library from the Decipher (Cellcta, Mountain View, CA, USA) and transduced into MDS-derived human cell lines. Transduced cell lines were treated with azacitidine, a first-line drug for MDS patients, for 30 days. Then, we isolated genomic DNA and detected specific barcode sequences for each shRNA plasmid with next-generation sequencing. By comparing the clonal composition with or without azacitidine treatment, we identified 158 candidate genes that may induce the azacitidine resistance in MDS.

Research Products

• [Journal Article] NF-κB/TNF-α positive feedback loop with active proteasome machinery supports myeloid leukemia initiating cell capacity (2014)
  • Author(s): Kagoya Y, Yoshimi A, Kataoka K, Nakagawa M, Kumano K, Arai S, Kobayashi H, Saito T, Iwakura Y, and Kurokawa M.
  • Journal Title: J Clin Invest Volume: 124(2) Pages: 528-542
• [Journal Article] Catheter-related septic shock by Micrococcus in an autologous hematopoietic stem cell transplantation recipient. (2014)
  • Author(s): Kogure Y, Nakamura F, Nukina A, Kamikubo Y, Ichikawa M, Kamikubo Y, and Kurokawa M.
  • Journal Title: Am J Infect Control Volume: 42(1) Pages: 87-87
• [Journal Article] Distribution of serum erythropoietin levels in lower risk myelodysplastic syndrome cases with anemia (2014)
  • Author(s): Nakazaki K, Nannya Y, and Kurokawa M.
  • Journal Title: Int J Hematol Volume: 99(1) Pages: 53-6
• [Journal Article] Single-cell gene expression analysis reveals clonal architecture of blast-phase chronic myeloid leukaemia (2014)
  • Author(s): Nukina A, Kagoya Y, Watanabe-Okochi N, Arai S, Ueda K, Yoshimi A, Nannya Y, and Kurokawa M.
  • Journal Title: Br J Haematol Volume: (Epub ahead of print)
• [Journal Article] Intracellular reactive oxygen species mark and influence the megakaryocyte-erythrocyte progenitor fate of common myeloid progenitors (2014)
  • Author(s): Shinohara A, Imai Y, Nakagawa M, Takahashi T, Ichikawa M, and Kurokawa M.
  • Journal Title: Stem Cells Volume: 32 Pages: 548-57
• [Journal Article] MALT lymphoma of the small bowel with protein-losing enteropathy (2014)
  • Author(s): Tsukamoto A, Nakamura F, Nannya Y, Kobayashi Y, Shibahara J, Ichikawa M, Fukayama M, Koike K, and Kurokawa M.
  • Journal Title: Int J Hematol Volume: Jan 7 (Epub ahead of print)
• [Journal Article] Pulmonary lymphocyte-rich classical Hodgkin lymphoma with early response to ABVD therapy. (2014)
  • Author(s): Honda A, Nakamura F, Nannya Y, Shintani Y, Fukayama M, Ichikawa M, and Kurokawa M.
  • Journal Title: Annals of Hematology Volume: 93 Issue: 6 Pages: 1073-1074
  • DOI: 10.1007/s00277-013-1935-6
  • Peer Reviewed
• [Journal Article] Positive feedback between NF-κB and TNF-α promotes leukemia-initiating cell capacity. (2014)
  • Author(s): Kagoya Y, Yoshimi A, Kataoka K, Nakagawa M, Kumano K, Arai S, Kobayashi H, Saito T, Iwakura Y, Kurokawa M.
  • Journal Title: J Clin Invest. Volume: 124 Issue: 2 Pages: 528-542
  • DOI: 10.1172/jci68101
  • Peer Reviewed
• [Journal Article] Distribution of serum erythropoietin levels in lower risk myelodysplastic syndrome cases with anemia. (2014)
  • Author(s): Nakazaki K, Nannya Y, and Kurokawa M.
  • Journal Title: Int J Hematol Volume: 99(1) Issue: 1 Pages: 53-56
  • DOI: 10.1007/s12185-013-1485-7
  • Peer Reviewed
• [Journal Article] Serial Profile of Vitamins and Trace Elements during the Acute Phase of Allogeneic Stem Cell Transplantation. (2014)
  • Author(s): Nannya Y, Shinohara A, Ichikawa M, and Kurokawa M.
  • Journal Title: Biology of Blood and Marrow Transplantation Volume: 20 Issue: 3 Pages: 430-434
  • DOI: 10.1016/j.bbmt.2013.12.554
  • Peer Reviewed
• [Journal Article] Development of hairy cell leukemia in familial platelet disorder with predisposition to acute myeloid leukemia. (2014)
  • Author(s): Toya T, Yoshimi A, Morioka T, Arai S, Ichikawa M, Usuki K, Kurokawa M
  • Journal Title: Platelets Volume: 25 Issue: 4 Pages: 300-302
  • DOI: 10.3109/09537104.2013.818636
  • Peer Reviewed
• [Journal Article] MALT lymphoma of the small bowel with protein-losing enteropathy. (2014)
  • Author(s): Tsukamoto A, Nakamura F, Nannya Y, Kobayashi Y, Shibahara J, Ichikawa M, Fukayama M, Koike K, and Kurokawa M.
  • Journal Title: International Journal of Hematology Volume: 99 Issue: 2 Pages: 198-201
  • DOI: 10.1007/s12185-013-1492-8
  • Peer Reviewed
• [Journal Article] Pulmonary lymphocyte-rich classical Hodgkin lymphoma with early response to ABVD therapy (2013)
  • Author(s): Honda A, Nakamura F, Nannya Y, Shintani Y, Fukayama M, Ichikawa M, and Kurokawa M.
  • Journal Title: Ann Hematol Volume: Oct 31 (Epub ahead of print)
• [Journal Article] Serial Profile of Vitamins and Trace Elements during the Acute Phase of Allogeneic Stem Cell Transplantation (2013)
  • Author(s): Nannya Y, Shinohara A, Ichikawa M, and Kurokawa M.
  • Journal Title: Biol Blood Marrow Transplant Volume: (Epub ahead of print)
• [Journal Article] A mixed-type autoimmune hemolytic anemia with immune thrombocytopenia related with myositis and post-transplantation lymphoproliferative disorder (2013)
  • Author(s): Ogura M, Ichikawa M, Masuda A, Kandabashi K, Nannya Y, and Kurokawa M.
  • Journal Title: Ann Hematol Volume: (Epub ahead of print)
• [Journal Article] Development of hairy cell leukemia in familial platelet disorder with predisposition to acute myeloid leukemia (2013)
  • Author(s): Toya T, Yoshimi A, Morioka T, Arai S, Ichikawa M, Usuki K, Kurokawa M.
  • Journal Title: Platelets Platelets Volume: Aug 23 (Epub ahead of print)
• [Journal Article] Transcription factor RUNX1 promotes survival of acute myeloid leukemia cells (2013)
  • Author(s): Goyama S, Schibler J, Cunningham L, Zhang Y, Rao Y, Nishimoto N, Nakagawa M, Olsson A, Wunderlich M, Link KA, Mizukawa B, Grimes HL, Kurokawa M, Liu PP, Huang G, and Mulloy JC.
  • Journal Title: J Clin Invest. Volume: 123 Pages: 3876-88
• [Journal Article] A role for RUNX1 in hematopoiesis and myeloid leukemia (2013)
  • Author(s): Ichikawa M, Yoshimi A, Nakagawa M, Nishimoto N, Watanabe-Okochi N, and Kurokawa M.
  • Journal Title: Int J Hematol Volume: 97 Pages: 726-34
  • NAID: 10031183728
• [Journal Article] Acute myeloid leukemia with cryptic CBFB-MYH11 type D (2013)
  • Author(s): Kobayashi T, Ichikawa M, Kamikubo Y, and Kurokawa M.
  • Journal Title: Int J Clin Exp Pathol Volume: 6 Pages: 110-2
• [Journal Article] The effect of decreased-dose idarubicin for elderly patients with acute myeloid leukemia (2013)
  • Author(s): Kobayashi T, Ichikawa M, Nannya Y, and Kurokawa M.
  • Journal Title: Jpn J Clin Oncol Volume: 43 Pages: 1047-51
• [Journal Article] Generation of iPS cells from normal and malignant hematopoietic cells (2013)
  • Author(s): Kumano K, Arai S, and Kurokawa M.
  • Journal Title: Int J Hematol Volume: 98 Pages: 145-52
  • NAID: 10031194728
• [Journal Article] Moxifloxacin is more effective than tosufloxacin in reducing chemotherapy-induced febrile neutropneia in patients with hematological malignancies (2013)
  • Author(s): Shinohara A, Yoshiki Y, Masamoto Y, Hangaishi A, Nannya Y, and Kurokawa M.
  • Journal Title: Leuk Lymphoma Volume: 54 Pages: 794-8
• [Journal Article] Simultaneous increase in 1,3-β-D-glucan and procalcitonin levels in Pseudomonas aeruginosa infection (2013)
  • Author(s): Koya J, Nannya Y, Kobayashi H, Okugawa S, Moriya K, and Kurokawa M.
  • Journal Title: J Infect Volume: 67 Pages: 164-6
• [Journal Article] Simple but powerful prognostic scoring model for MALT lymphoma : a retrospective study. (2013)
  • Author(s): Morita K, Nannya Y, Yoshizato T, and Kurokawa M.
  • Journal Title: Ann Hematol Volume: 92 Pages: 421-3
• [Journal Article] Unique association of Waldenstrom macroglobulinemia with optic neuritis and monoclonal T cell expansion. (2013)
  • Author(s): Morita K, Yoshimi A, MasudaA, Ichikawa M, Yatomi Y, and Kurokawa M.
  • Journal Title: Int J Hematol Volume: 98 Pages: 247-9
  • NAID: 10031194743
• [Journal Article] A case of Schizophyllum commune sinusitis following unrelated cord blood transplantation for acute lymphoblastic leukemia (2013)
  • Author(s): Toya T, Shinohara A, Tatsuno K, Seo S, Nannya Y, Ichikawa M, Makimura K, Moriya K, and Kurokawa M.
  • Journal Title: Int J Hematol Volume: 98 Pages: 261-3
  • NAID: 10031194746
• [Journal Article] Successful treatment with recombinant thrombomodulin for B-cell lymphoma-associated hemophagocytic syndrome complicated by disseminated intravascular coagulation (2013)
  • Author(s): Uni M, Yoshimi A, Maki H, Maeda D, Nakazaki K, Nakamura F, Fukayama M, and Kurokawa M.
  • Journal Title: Int J Clin Exp Pathol Volume: 6 Pages: 1190-4
  • NAID: 120007089059
• [Journal Article] Transformation of follicular lymphoma in the retroperitoneal muscles demonstrated by CT-guided needle biopsy of FDG-avid lesions; case series (2013)
  • Author(s): Uni M, Nakamura F, Yoshimi A, Shinozaki-Ushiku A, Hosoi A, Nakazaki K, Nannya Y, Fukayama M, and Kurokawa M.
  • Journal Title: Int J Clin Exp Pathol Volume: 7 Pages: 402-6
• [Journal Article] Catheter-related septic shock by Micrococcus in an autologous hematopoietic stem cell transplantation recipient (2013)
  • Author(s): Kogure Y, Nakamura F, Nukina A, Kamikubo Y, Ichikawa M, Kurokawa M, Kamikubo Y, Kurokawa M
  • Journal Title: Am J Infect Control. Volume: 42 Issue: 1 Pages: 87-87
  • DOI: 10.1016/j.ajic.2013.07.010
  • Peer Reviewed
• [Journal Article] Single-cell gene expression analysis reveals clonal architecture of blast-phase chronic myeloid leukaemia. (2013)
  • Author(s): Nukina A, Kagoya Y, Watanabe-Okochi N, Arai S, Ueda K, Yoshimi A, Nannya Y, and Kurokawa M.
  • Journal Title: Br J Haematol Volume: In Press Issue: 3 Pages: 580-91
  • DOI: 10.1111/bjh.12726
  • Peer Reviewed
• [Journal Article] A mixed-type autoimmune hemolytic anemia with immune thrombocytopenia related with myositis and post-transplantation lymphoproliferative disorder. (2013)
  • Author(s): Ogura M, Ichikawa M, Masuda A, Kandabashi K, Nannya Y, and Kurokawa M.
  • Journal Title: Ann Hematol. Volume: In Press Issue: 5 Pages: 869-871
  • DOI: 10.1007/s00277-013-1887-x
  • Peer Reviewed
• [Journal Article] Intracellular reactive oxygen species mark and influence the megakaryocyte-erythrocyte progenitor fate of common myeloid progenitors. (2013)
  • Author(s): Shinohara A, Imai Y, Nakagawa M, Takahashi T, Ichikawa M, and Kurokawa M.
  • Journal Title: Stem Cells Volume: 32 Issue: 2 Pages: 548-557
  • DOI: 10.1002/stem.1588
  • Peer Reviewed
• [Journal Article] Transcription factor RUNX1 promotes survival of acute myeloid leukemia cells. (2013)
  • Author(s): Goyama S, Schibler J, Cunningham L, Zhang Y, Rao Y, Nishimoto N, Nakagawa M, Olsson A, Wunderlich M, Link KA, Mizukawa B, Grimes HL, Kurokawa M, Liu PP, Huang G, and Mulloy JC.
  • Journal Title: J Clin Invest Volume: 123 Issue: 9 Pages: 3876-3888
  • DOI: 10.1172/jci68557
  • Peer Reviewed
• [Journal Article] A role for RUNX1 in hematopoiesis and myeloid leukemia. (2013)
  • Author(s): Ichikawa M, Yoshimi A, Nakagawa M, Nishimoto N, Watanabe-Okochi N, and Kurokawa M.
  • Journal Title: Int J Hematol Volume: 97 Issue: 6 Pages: 726-734
  • DOI: 10.1007/s12185-013-1347-3
  • NAID: 10031183728
  • Peer Reviewed
• [Journal Article] Acute myeloid leukemia with cryptic CBFB-MYH11 type D. (2013)
  • Author(s): Kobayashi T, Ichikawa M, Kamikubo Y, and Kurokawa M.
  • Journal Title: International Journal of Clinical and Experimental Pathology Volume: 6 Pages: 110-112
  • Peer Reviewed
• [Journal Article] The effect of decreased-dose idarubicin for elderly patients with acute myeloid leukemia. (2013)
  • Author(s): Kobayashi T, Ichikawa M, Nannya Y, and Kurokawa M.
  • Journal Title: Jpn J Clin Oncol Volume: 43 Issue: 10 Pages: 1047-1051
  • DOI: 10.1093/jjco/hyt111
  • Peer Reviewed
• [Journal Article] Generation of iPS cells from normal and malignant hematopoietic cells. (2013)
  • Author(s): Kumano K, Arai S, Kurokawa M.
  • Journal Title: Int J Hematol. Volume: 98 Issue: 2 Pages: 145-182
  • DOI: 10.1007/s12185-013-1385-x
  • NAID: 10031194728
  • Peer Reviewed
• [Journal Article] Moxifloxacin is more effective than tosufloxacin in reducing chemotherapy-induced febrile neutropneia in patients with hematological malignancies. (2013)
  • Author(s): Shinohara A, Yoshiki Y, Masamoto Y, Hangaishi A, Nannya Y, and Kurokawa M.
  • Journal Title: Leuk Lymphoma Volume: 54 Issue: 4 Pages: 794-798
  • DOI: 10.3109/10428194.2012.725848
  • Peer Reviewed
• [Journal Article] Simultaneous increase in 1,3-β-D-glucan and procalcitonin levels in Pseudomonas aeruginosa infection. (2013)
  • Author(s): Koya J, Nannya Y, Kobayashi H, Okugawa S, Moriya K, Kurokawa M.
  • Journal Title: J Infect Volume: 67 Issue: 2 Pages: 164-166
  • DOI: 10.1016/j.jinf.2013.03.017
  • Peer Reviewed
• [Journal Article] Simple but powerful prognostic scoring model for MALT lymphoma: a retrospective study. (2013)
  • Author(s): Morita K, Nannya Y, Yoshizato T, Kurokawa M.
  • Journal Title: Ann Hematol Volume: 92 Issue: 3 Pages: 421-423
  • DOI: 10.1007/s00277-012-1585-0
  • Peer Reviewed
• [Journal Article] Unique association of Waldenström macroglobulinemia with optic neuritis and monoclonal T cell expansion. (2013)
  • Author(s): Morita K, Yoshimi A, Masuda A, Ichikawa M, Yatomi Y, Kurokawa M.
  • Journal Title: Int J Hematol Volume: 98 Issue: 2 Pages: 247-249
  • DOI: 10.1007/s12185-013-1372-2
  • Peer Reviewed
• [Journal Article] A case of Schizophyllum commune sinusitis following unrelated cord blood transplantation for acute lymphoblastic leukemia. (2013)
  • Author(s): Toya T, Shinohara A, Tatsuno K, Seo S, Nannya Y, Ichikawa M, Makirnura K Moriya K, Kurokawa M
  • Journal Title: lnternational Journal of Hematology Volume: 98 Issue: 2 Pages: 261-263
  • DOI: 10.1007/s12185-013-1362-4
  • Peer Reviewed
• [Journal Article] Successful treatment with recombinant thrombomodulin for B-cell lymphoma-associated hemophagocytic syndrome complicated by disseminated intravascular coagulation. (2013)
  • Author(s): Uni M, Yoshimi A, Maki H, Maeda D, Nakazaki K, Nakamura F, Fukayama M, and Kurokawa M.
  • Journal Title: International Journal of Clinical and Experimental Pathology Volume: 6 Pages: 1190-1194
  • NAID: 120007089059
  • Peer Reviewed
• [Journal Article] Transformation of follicular lymphoma in the retroperitoneal muscles demonstrated by CT-guided needle biopsy of FDG-avid lesions; case series. (2013)
  • Author(s): Uni M, Nakamura F, Yoshimi A, Shinozaki-Ushiku A, Hosoi A, Nakazaki K, Nannya Y, Fukayama M, and Kurokawa M
  • Journal Title: International Journal of Clinical and Experimental Pathology Volume: 7 Pages: 402-406
  • Peer Reviewed