Myeloproliferative stem cell disorders by deregulated Rap1 activation in SPA-1-deficient mice

Daisuke Ishida, Kohei Kometani, Hailin Yang, Kiyokazu Kakugawa, Kyoko Masuda, Kazuhiro Iwai, Misao Suzuki, Shigeyoshi Itohara, Tatsutoshi Nakahata, Hiroshi Hiai, Hiroshi Kawamoto, Masakazu Hattori, Nagahiro Minato

研究成果: Article査読

110 被引用数 (Scopus)

抄録

SPA-1 (signal-induced proliferation-associated gene-1) is a principal Rap1 GTPase-activating protein in hematopoietic progenitors. SPA-1-deficient mice developed a spectrum of myeloid disorders that resembled human chronic myelogenous leukemia (CML) in chronic phase, CML in blast crisis, and myelodysplastic syndrome as well as anemia. Preleukemic SPA-1-deficient mice revealed selective expansion of marrow pluripotential hematopoietic progenitors, which showed abnormal Rap1GTP accumulation. Overexpression of an active form of Rap1 promoted the proliferation of normal hematopoietic progenitors, while SPA-1 overexpression markedly suppressed it. Furthermore, restoring SPA-1 gene in a SPA-1-deficient leukemic blast cell line resulted in the dissolution of Rap1GTP accumulation and concomitant loss of the leukemogenicity in vivo. These results unveiled a role of Rap1 in myeloproliferative stem cell disorders and a tumor suppressor function of SPA-1.

本文言語English
ページ(範囲)55-65
ページ数11
ジャーナルCancer Cell
4
1
DOI
出版ステータスPublished - 01-07-2003
外部発表はい

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 細胞生物学
  • 癌研究

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