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Differentiation-induction of all-trans retinoic acid in acute promyelocytic leukemia

Research Project

Project/Area Number 07670836
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionTohoku University

Principal Investigator

IMAIZUMI Masue  Department of Pediatrics, Tohoku University School of Medicine, Assistant Professor, 医学部, 講師 (40191895)

Co-Investigator(Kenkyū-buntansha) SUZUKI Hoshiro  Dept. of Pediatrics, Tohoku Univ. School of Medicine, Clinical Instructor, 医学部・附属病院, 医員
IDE Hiroyuki  Dept. of Biology, Molecular and cell Biology Division, Tohoku Univ. School of Sc, 理学部, 教授 (70022704)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1995: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsAPL / ATRA / Differentiation / PML / RARalpha / apoptosis / RT-PCR
Research Abstract

(1) We investigated the evidence of apoptosis during all-trans retinoic acid (ATRA) therapy in three patients with acute promyelocytic leukemia (APL). Blood cells derived from the patients in vivo showed DNA fragmentation transitionally in the phase of regression of hyperleukocytosis, the majority of which were mature yet aberrant granulocytes of APL clone origin. Furthermore, morphological features of apoptosis were also demonstrated in a small fraction of cells simultaneously with the appearance of DNA fragmentation in two patients who received adjunctive chemotherapy in addition to ATRA therapy. These findings suggest that APL cells, even if in a small fraction, may undergo apoptosis while differentiating in vivo with ATRA therapy, and that rapid clearance of leukemic cells from the patient's blood may be attributed to apoptotic cell death of APL cells.
(2) We studied the disease monitoring of nine patients with APL by detecting PML/RARalpha mRNA fusion points using RT-PCR combined with ASO.Patients (four males and five females) were 8.3 years of mean age (a range from four to fifteen years old) with an average observation period of 30 months (a range from 18 to 52 months). After obtaining complete remission with ATRA therapy, six patients received multidrug-combined chemotherapy (group A), in whom bone marrow transplantation (BMT) was performed later in three patients during first remission and in one after BM relapse. The rest of three patients received an alternatively combined therapy with chemotherapeutic agents and ATRA (group B), from whom one relapsed and died in refractory state. This method of disease monitoring could identified a high risk of one patient in group A who showed a shift of MRD positivity from nested to single PCR levels, however, it was not informative for another in group B who relapse at fifteen months from onset.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Sato A,Imaizui M et al.: "Acute myelogenous leukaemia with t(8;21)translocation of normal cell origin in mosaic Down's syndrome with isochromosome 21q" British J Haematology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Singh N,Takahashi S et al.: "Treatment-related disseminated necrotizing leukoencephalopathy with characteristic contrast enhancement of the white matter" Radiation Medicine. 14. 303-307 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Morita S,Tsuchiya S et al.: "Cell surface c-kit receptors in human leukemia cell lines and pediatric leukemia : selective preservation of c-kit expression on megakaryoblastic cell lines during adaptation to in vitro culture" Leukemia. 10. 102-105 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sato A,Imaizumi M et al.: "Aberrant progenitors common to megakaryocytic and myeloid cells in a Down's infant with transient abnormal myelopoiesis" Leukemia Research. 19. 811-815 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Matsumoto K,Takahashi S et al.: "Leukoencephalopathy in childhood hematopoietic neoplasm caused by moderate-dose methotrexate and prophylactic cranial radiotherapy-an MR analysis" Int Radiation Oncology Biol.Phys.32. 913-918 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 畑江芳郎、中館尚也 他: "All-trans retinoic acid (ATRA)により寛解導入に成功した急性前骨髄性白血病" 臨床血液. 37. 1410-1415 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 荒井宏治、伊藤悦朗 他: "乳児白血病の臨床解析-予後因子の検討-" 日本小児血液学会雑誌. 10. 344-350 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 佐藤 篤、今泉益栄 他: "抗NA2抗体による同種免疫性好中球減少症の1例" 日本小児血液学会雑誌. 10. 194-198 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 服部浩佳、堀越康雄 他: "Cyclophosphamide,total body irradiation,total lymphoid irradiationおよびantithymocyte globulinの前処理にて非血縁者間骨髄移植を行った重症型再生不良性貧血の1例" 日本小児血液学会雑誌. 10. 127-131 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 伊藤経夫、田村 真 他: "末梢血幹細胞採取における心電図監視の必要性を認めた1例" 日本輸血学会雑誌. 41. 617-621 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 今泉益栄: "リソソーム蓄積病の骨髄移植" 日本臨床. 53. 203-208 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sato A,Imaizumi M et al.: "Acute myelogenous leukaemia with t(8 ; 21) translocation of normal cell origin in mosaic Down's syndrome with isochromosome 21q." British J Haematology. 96. 614-616 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Singh N,Takahashi S et al.: "Treatment-related disseminated necrotizing leukoencephalopathy with characteristic contrast enhancement of the white matter." Radiation Medicine. 14. 303-307 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Morita S,Tsuchiya S et al.: "Cell surface c-kit receptors in human leukemia cell lines and pediatric leukemia : selective preservation of c-kit expression on megakaryoblastic cell lines during adaptation to in vitro culture." Leukemia. 10. 102-105 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sato A,Imaizumi M et al.: "Aberrant progenitors common to megakaryocytic and myeloid cells in a Down's infant with transient abnormal myelopoiesis." Leukemia Research. 19. 811-815 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Matsumoto K,Takahashi S et al.: "Leukoencephalopathy in childhood hematopoietic neoplasm caused by moderate-dose methotrexate and prophylactic radiotherapy-An MR analysis." Int J Radi Oncolo Bio Phys. 32. 913-918 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sato A, Imaizumi M et al.: "Acute myelogenous leukaemia with t (8; 21) translocation of normal cell origin in mosaic Down's syndrome with isochromosome 21q" British J Haematology. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Singh N, Takahashi S et al.: "Treatment-related disseminated necrotizing leukoencephalopathy with characteristic contrast enhancement of the white matter" Radiation Medicine. 14. 303-307 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Morita S, Tsuchiya S et al.: "Cell surface c-kit receptors in human leukemia cell lines and pediatric leukemia: selective preservation of c-kit expression on megakaryoblastic cell lines during adaptation to in vitro culture" Leukemia. 10. 102-105 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 佐藤 篤、今泉益栄 他: "抗NA2抗体による同種免疫性好中球減少症の1例" 日本小児血液学会雑誌. 10. 194-198 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 服部浩佳、堀越康雄 他: "Cyclophosphamide, total body irradiation, total lymphoid irradiation および antithymocyte globulin の前処置にて非血縁者間骨髄移植を行った重症型再生不良性貧血の1例" 日本小児血液学会雑誌. 10. 127-131 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 畑江芳郎、中館尚也 他: "All-trans retinoic acid (ATRA) により寛解導入に成功した急性前骨髄性白血病" 臨床血液. 37. 1410-1415 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 荒井宏治、伊東悦朗 他: "乳児白血病の臨床解析-予後因子の検討-" 日本小児血液学会雑誌. 10. 344-350 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Morita S. er al: "Cell surface c-kit receptor in human leukemia cell lines and pediatric leukemia : selective presentation of c-kit expression on megakaryoblastic cell lines during adaptation to in vitro cultue." Leukemia. 10. 102-105 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Sato A. et all: "Aberrant progenitors common to megakaryocytic and myeloid cells in a Down's infant with transient abnormal myelopoiesis." Leukemia Res.19. 811-815 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Matsumoto K. et all: "Leukoencephalopathy in childhood hematopoietic neoplasm caused by moderate-dose methotrexate and prophylactic cranial radiotherapy-An MR analysis." Int J Radi Oncol Bio Phys.32. 913-918 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 今泉益栄: "リソソーム蓄積病の骨髄移植." 日本臨床. 53. 203-208 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Imaizumi M. et all: "Protentiated maturation with a high proliferating activity of acute promyelocytic leukemia induced in vitro by granulocyte or granulocyte/macrophage colony-stimulating factors in combination with all-trans retinoic acid." Leukemia. 8. 1301-1308 (1994)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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