The biologic properties of recombinant human thrombopoietin in the proliferation and megakaryocytic differentiation of acute myeloblastic leukemia cells

Itaru Matsumura, Yuzuru Kanakura*, Takashi Kato, Hirokazu Ikeda, Yoko Horikawa, Jun Ishikawa, Hitoshi Kitayama, Tetsuo Nishiura, Yoshiaki Tomiyama, Hiroshi Miyazaki, Yuji Matsuzawa

*この研究の対応する著者

研究成果: Article査読

35 被引用数 (Scopus)

抄録

Thrombopoietin (TPO) is implicated as a primary regulator of megakaryopoiesis and thrombopoiesis. However, the biologic effects of TPO on human acute myeloblastic leukemia (AML) cells are largely unknown. To determine if recombinant human (rh) TPO has proliferation-supporting and differentiation-inducing activities in AML cells, 15 cases of AML cells that were exclusively composed of undifferentiated leukemia cells and showed growth response to rhTPO in a short-term culture (72 hours) were subjected to long-term suspension culture with or without rhTPO. Of 15 cases, rhTPO supported proliferation of AML cells for 2 to 4 weeks in 4 cases whose French-American-British subtypes were M0, M2, M4, and M7, respectively. In addition to the proliferation-supporting activity, rhTPO was found to induce AML cells to progress to some degree of megakaryocytic differentiation at both morphologic and surface-phenotypic levels in 2 AML cases with M0 and M7 subtypes. The treatment of AML cells with rhTPO resulted in rapid tyrosine phosphorylation of the TPO-receptor, c-mpl, and STAT3 in all of cases tested. By contrast, the expression of erythroid/megakaryocyte-specific transcription factors (GATA-1, GATA-2, and NF-E2) was markedly induced or enhanced in only 2 AML cases that showed megakaryocytic differentiation in response to rhTPO. These results suggested that, at least in a fraction of AML cases, TPO could not only support the proliferation of AML cells irrespective of AML subtypes, but could also induce megakaryocytic differentiation, possibly through activation of GATA-1, GATA-2, and NF-E2.

本文言語English
ページ(範囲)3074-3082
ページ数9
ジャーナルBlood
88
8
DOI
出版ステータスPublished - 1996 10 15
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 免疫学
  • 血液学
  • 細胞生物学

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