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Hairy B-cell lymphoproliferative disorder, and differentiation and proliferation of the B-cells

Research Project

Project/Area Number 10670948
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionOsaka University Graduate School of Medicine

Principal Investigator

MACHII Takashi  Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (50124780)

Co-Investigator(Kenkyū-buntansha) SHIBANO Masaru  Osaka University Hospital, Medical stuff, 医学部・附属病院, 医員
IKEDA Hirokazu  Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助手 (10311755)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsHairy cell leukemia / B cell lymphocytosis / lymphoproliferative disorder / clonality / ubiquitin / apoptosis / Rho / cell mozphology / ヘアリー細胞白血病 / B細胞 / ユビキチン / 造血抑制 / リンパ球増加症 / clonality / 免疫グロブリン / 決色体
Research Abstract

Hairy B-cell lymphoproliferative disorder (HBLD) is a new disease entity, characterized by chronic polyclonal B-cell lymphocytosis with features resembling hairy cell leukemia (HCL)-Japanese variant.
1. Various cytokines and mitogens failed to induce proliferation and differentiation in B-cells in HBLD (HBLD cells) but TNFα and SAC, which slishtly enhanced the ^3H tymidine uptake.
2. HBLD cells did not differentiate into Ig-secreting cells by phorbol ester (TPA), but changed their shape into fibroblast-like cells, as described for HCL cells. Y27632, an inhibitor of ROCK, suppressed this transformation. We also studied effects of wortmannin, a PI3 kinase inhibitor, on the morphology of HCL cells and HBLD cells. The studies suggested association of Rho and Rac/Cdc42 with the characteristic morphology of these cells.
3. We previously showed that ubiquitin (Ub) was secreted from HCL cells and had inhibitory effects on normal hematopoiesis. In this study, we investigated effects of extracellar … More Ub on various hematopoietic cell lines. The results suggested that extracellar Ub incorporated into hematopoitic cells and mediated growth suppression and apoptosis through a proteasome-dependent manner. We also found that serum Ub levels were higher in patients with HBLD than in normal volunteers, suggesting that Ub may be involved in anemia and/or thrombopenia seen in those with HBLD.On the other hand, Ub showed no effect on differentiation and proliferation of HBLD cells.
4. Clinical and hematological resemblance of HBLD and HCL-Japanese variant suggests that HBLD may transform into HCL.We detected small B-cell clones in peripheral blood lymphocytes or spleen cells from two of 7 patients with HBLD by PCR.Chromosomal abnormality was detected in one patient. The B-ceLl clones persisted, but expansion of the clones was not seen.
5. Attempts were made to detect known or unknown viruses, and immunological abnormalities including those of cytokines in HBLD, but we could not find any causative factor of the disease. Less

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] 待井隆志: "Hairy cell leukemia"臨床医. 27・4. 40-41 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 神林裕行: "Hairy cell leukemia 類似の臨床像および血液所見を示こにpolyclonal B-cell lymphocytosis."臨床血液. 39・7. 493-498 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 待井隆志: "リンパ球増多症"内科. 81・6. 1140-1141 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hirokagu Tanaka: "GATA.1 blcks IL-6-induced macrophage differentiation and apoptosis through the sustained expression of cyclin D1 and Bel-2 in a murine myeloid cell line M1."Blood. 95・4. 1264-1273 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Maki Kuwayama: "Blastic transformation of splenic lymophema with nillous iymphecytes oftes a well-controlled chionic phase of more than ten years"Int J Hematol. (in print).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hanako Daino: "Induction of apoptosis by extracellulan ubiguitin in human hematopoietic cells."Blood. (in print).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 待井隆志: "Annual Review 血液 2000"高久史磨他編,中外医学社. 270 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takashi Machii: "Hairy cell leukemia."Rinnshoui. 27(4). 40-41 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hiroyuki Kannbayashi et al.: "Polyclonal B-cell lymphocytosis with clinical and hematological features resembling hairy cell leukemia."Rinnsho-Ketsueki. 39(7). 493-468 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takashi Machii: "Lymphocytosis."Naika. 81(6). 1140-1141 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hiroyuki Tanaka et al.: "GATA-1 blocks IL-6-induced macrophage differentiation and apoptosis through the sustained expression of cyclin D1 and Bcl-2 in a murine myeloid cell line M1."Blood. 95(4). 1264-1273 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Maki Kuwayama et al.: "Blastic transformation of splenic lymphoma with villous lymphocytes after a well-controlled chronic phase of more than ten years."Int J Hematol. (in print).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hanako Daino et al.: "Induction of apoptosis by extracellular ubiquitin in hematopoietic cells : possible involvement of STAT3 degradation by proteasome pathway in interleukin 6-dependent hematopoietic cells."Blood. (in print).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 待井隆志: "表面マーカーによる診断"医学のあゆみ. 190・5. 441-445 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 待井隆志: "ヘアリーセル白血病"血液腫瘍科. 39・4. 261-265 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 待井隆志: "慢性リンパ性白血病の診断と分類"内科. 84・3. 429-431 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Daino Hanako: "Induction of apoptosis by extracellular ubiquitin in human hematopoietic cells"Blood. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 待井隆志: "Annual Review 血液 2000 (高久史麿他編)"中外医学社. 270 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 神林裕行: "Hairy cell leukemia 類似の臨床像および血液学的所見を示したpolyclonal B-cell lymphocytosis" 臨床血液. 39・7. 493-498 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 待井隆志: "Hairy cell leukemia." 臨床医. 24・7. 40-41 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 待井隆志: "慢性リンパ性白血病(CLL)と類縁疾患" Biomedical Perspectires. 7・1. 4-8 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Mizuki Masao: "Phenotypical hetezogeneity of CD4+CD8+ double-positive chronic T lymphoid leukemia." Leukemia. 12・4. 499-504 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shibano Masaru: "Assesment of alkaline phosphatase on the sanface membrane of neutrophils by immun of Cudrescence." Am J Hematology. 60・1. 12-18 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Azenichi: "CD54-deficient blood cells and PIG-A gene θbnormalities in Japanese patients with aplastic θnaemia" Br J Haematology. in press. (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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