The role of polycomb complex on the clonal evolution in myelodysplastic syndrome

• Project/Area Number: 25893049
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Hematology
• Research Institution: The University of Tokyo
• Principal Investigator: TAKAAKI konuma 東京大学, 医科学研究所, 助教 (00709553)
• Project Period (FY): 2013-08-30 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 骨髄異形成症候群 / ポリコーム

Outline of Final Research Achievements

Myelodysplastic syndrome (MDS) has a varied clinical course, with some patients remaining asymptomatic with mild cytopenia for a long time, while others show progressive leukemia a short time after the diagnosis. In the present study, we analyzed whether epigenetic alternation could contribute to the disease progression of MDS. It is suggested that alteration of oncogene expression is regulated by histone modification. This study suggested a new role of epigenetic alternation in the disease progression of MDS and possibilities of these processes as new targets of novel molecular therapy.

Research Products

• [Journal Article] Long-term outcomes of granulocyte colony-stimulating factor-combined conditioning in allogeneic hematopoietic stem cell transplantation from HLA-identical family donors for myeloid malignancies. (2015)
  • Author(s): Konuma T, Kato S, Ishii H, Oiwa-Monna M, Asano S, Tojo A, Takahashi S.
  • Journal Title: Leuk Res Volume: In press Issue: 6 Pages: 625-631
  • DOI: 10.1016/j.leukres.2015.03.022
  • Peer Reviewed
• [Journal Article] Fbxl10 overexpression in murine hematopoietic stem cells induces leukemia involving metabolic activation and upregulation of Nsg2. (2015)
  • Author(s): Ueda T, Nagamachi A, Takubo K, Yamasaki N, Matsui H, Kanai A, Nakata Y, Ikeda K, Konuma T, Oda H, Wolff L, Honda ZI, Wu X, Helin K, Iwama A, Suda T, Inaba T, Honda H.
  • Journal Title: Blood Volume: In press
  • Peer Reviewed
• [Journal Article] HLA-DRB1 mismatch is associated with a decreased relapse in adult acute myeloid leukemia after single-unit myeloablative cord blood transplantation. (2015)
  • Author(s): Konuma T, Kato S, Ishii H, Takeda R, Oiwa-Monna M, Tojo A, Takahashi S.
  • Journal Title: Ann Hematol Volume: In press
  • Peer Reviewed
• [Journal Article] Third allogeneic stem cell transplantation (SCT) using unrelated cord blood for relapsed acute leukemia after second allogeneic SCT (2015)
  • Author(s): Konuma T, Kato S, Ooi J, Ebihara Y, Mochizuki S, Oiwa-Monna M, Tojo A, Takahashi S.
  • Journal Title: International journal of hematology. Volume: 101 Issue: 4 Pages: 392
  • DOI: 10.1007/s12185-015-1755-7
  • Peer Reviewed / Open Access
• [Journal Article] Clearance of blasts from peripheral blood during induction chemotherapy using exponential decay model predicts complete remission and long-term survival in adult acute myeloid leukemia (2015)
  • Author(s): Konuma T, Kato S, Yuji K, Ohno N, Uchimaru K, Takahashi S, Tojo A.
  • Journal Title: Int J Lab Hematol. Volume: - Issue: 3
  • DOI: 10.1111/ijlh.12302
  • Peer Reviewed
• [Journal Article] Myeloablative unrelated cord blood transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia: comparison with other graft sources from related and unrelated donors (2015)
  • Author(s): Konuma T, Kato S, Ooi J, Oiwa-Monna M, Tojo A, Takahashi S.
  • Journal Title: Ann Hematol Volume: 94 Issue: 2 Pages: 289
  • DOI: 10.1007/s00277-014-2195-9
  • Peer Reviewed
• [Journal Article] Single-unit cord blood transplant for acute lymphoblastic leukemia and lymphoma using an intensified conditioning regimen of total body irradiation, high-dose cytarabine and cyclophosphamide. (2015)
  • Author(s): Konuma T, Kato S, Oiwa-Monna M, Tojo A, Takahashi S.
  • Journal Title: Leuk Lymphoma Volume: In press
  • Peer Reviewed
• [Journal Article] Granulocyte colony-stimulating factor combined regimen in cord blood transplantation for acute myeloid leukemia: A nationwide retrospective analysis in Japan (2014)
  • Author(s): 1.Konuma T, Ooi J, Uchida N, Ogawa H, Ohashi K, Kanamori H, Aotsuka N, Onishi Y, Yamaguchi H, Kozai Y, Nagamura-Inoue T, Kato K, Suzuki R, Atsuta Y, Kato S, Asano S, Takahashi S.
  • Journal Title: Haematologica Volume: 99 Issue: 12 Pages: e264-e268
  • DOI: 10.3324/haematol.2014.114504
  • Peer Reviewed / Open Access
• [Journal Article] Hemorrhagic hepatic cyst after allogeneic bone marrow transplantation. (2014)
  • Author(s): Kato S, Konuma T, Tojo A, Takahashi S.
  • Journal Title: Int J Hematol Volume: 100 Issue: 3 Pages: 214-215
  • DOI: 10.1007/s12185-014-1640-9
  • Peer Reviewed
• [Journal Article] Comparable Long-Term Outcome of Unrelated Cord Blood Transplantation with Related Bone Marrow or Peripheral Blood Stem Cell Transplantation in Patients Aged 45 Years or Older with Hematologic Malignancies after Myeloablative Conditioning (2014)
  • Author(s): Konuma T, Kato S, Ooi J, Oiwa-Monna M, Kawamata T, Tojo A, Takahashi S
  • Journal Title: Biol Blood Marrow Transplant Volume: 20 Issue: 8 Pages: 1150
  • DOI: 10.1016/j.bbmt.2014.04.005
  • Peer Reviewed
• [Journal Article] Impact of sex incompatibility on the outcome of single-unit cord blood transplantation for adult patients with hematological malignancies (2014)
  • Author(s): Konuma T, Tojo A, et al.
  • Journal Title: Bone Marrow Transplant. Volume: 49 Issue: 5 Pages: 634
  • DOI: 10.1038/bmt.2014.10
  • Peer Reviewed / Open Access
• [Journal Article] The TIF1β-HP1 System Maintains Transcriptional Integrity of Hematopoietic Stem Cells. (2014)
  • Author(s): Miyagi S, Koide S, Saraya A, Wendt GR, Oshima M, Konuma T, Yamazaki S, Mochizuki-Kashio M, Nakajima-Takagi Y, Wang C, Chiba T, Kitabayashi I, Nakauchi H, Iwama A.
  • Journal Title: Stem Cell Reports. Volume: 2 Issue: 2 Pages: 145-52
  • DOI: 10.1016/j.stemcr.2013.12.008
  • Peer Reviewed / Open Access
• [Journal Article] Lis1 regulates asymmetric division in hematopoietic stem cells and in leukemia. (2014)
  • Author(s): Zimdahl B, Ito T, Blevins A, Bajaj J, Konuma T, Weeks J, Koechlein CS, Kwon HY, Arami O, Rizzieri D, Broome HE, Chuah C, Oehler VG, Sasik R, Hardiman G, Reya T.
  • Journal Title: Nat Genet. Volume: 46(3) Issue: 3 Pages: 245-52
  • DOI: 10.1038/ng.2889
  • Peer Reviewed
• [Journal Article] Effect of ABO blood group incompatibility on the outcome of single-unit cord blood transplantation after myeloablative conditioning (2014)
  • Author(s): Konuma T, Tojo A, et al.
  • Journal Title: Biol Blood Marrow Transplant. Volume: 20 Issue: 4 Pages: 577
  • DOI: 10.1016/j.bbmt.2013.12.563
  • Peer Reviewed / Open Access
• [Journal Article] Single-unit cord blood transplantation after granulocyte colony-stimulating factor-combined myeloablative conditioning for myeloid malignancies not in remission (2014)
  • Author(s): Konuma T, Tojo A, et al.
  • Journal Title: Biol Blood Marrow Transplant. 20(3): Volume: 20 Issue: 3 Pages: 396
  • DOI: 10.1016/j.bbmt.2013.12.555
  • Peer Reviewed
• [Journal Article] Pretransplant hyperferritinemia has no effect on the outcome of myeloablative cord blood transplantation for acute leukemia and myelodysplastic syndrome. (2013)
  • Author(s): Konuma T, Kato S, Oiwa-Monna M, Tojo A, Takahashi S.
  • Journal Title: Ann Hematol Volume: In press