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

被引：117

作者：

Ishida, D

Kometani, K

Yang, HL

Kakugawa, K

Masuda, K

Iwai, K

Suzuki, M

Itohara, S

Nakahata, T

Hiai, H

Kawamoto, H

Hattori, M

Minato, N ^{[1
]}

机构：

[1] Kyoto Univ, Grad Sch Biostudies, Dept Immunol & Cell Biol, Kyoto 6068501, Japan

[2] Kyoto Univ, Grad Sch Med, Dept Pediat, Kyoto 6068501, Japan

[3] Kyoto Univ, Grad Sch Med, Dept Pathol, Kyoto 6068501, Japan

[4] Kumamoto Univ, Ctr Anim Resources & Dev, Kumamoto 8620976, Japan

[5] RIKEN, Brain Sci Inst, Saitama 3510198, Japan

[6] RIKEN, Res Ctr Immunol & Allergy, Yokohama, Kanagawa 2300045, Japan

来源：

CANCER CELL | 2003年 / 4卷 / 01期

关键词：

D O I：

10.1016/S1535-6108(03)00163-6

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：55 / 65

页数：11

共 56 条

[1] Rap1 is activated by erythropoietin or interleukin-3 and is involved in regulation of β1 integrin-mediated hematopoietic cell adhesion [J].