Inhibition of granulocyte-macrophage colony-stimulating factor prevents dissemination and induces remission of juvenile myelomonocytic leukemia in engrafted immunodeficient mice.
Inhibition of granulocyte-macrophage colony-stimulating factor prevents dissemination and induces remission of juvenile myelomonocytic leukemia in engrafted immunodeficient mice.
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粒细胞-巨噬细胞集落刺激因子的抑制可防止移植的免疫缺陷小鼠中幼年粒单核细胞白血病的传播并诱导其缓解。
DOI：
10.1182/blood.v90.12.4910
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发表时间：
1997
期刊：
影响因子：
20.3
通讯作者：
A. Lopez
中科院分区：
文献类型：
--
作者：
P. Iversen;I. Lewis;S. Turczynowicz;H. Hasle;C. Niemeyer;K. Schmiegelow;S. Bastiras;A. Biondi;T. Hughes;A. Lopez
粒细胞-巨噬细胞集落刺激因子(GM-CSF)和肿瘤坏死因子α(TNFα)与幼年性粒单核细胞白血病(JMML)的发病机制密切相关。采用免疫缺陷/非肥胖严重联合糖尿病(SCID/NOD)小鼠模型，观察了人GM-CSF拮抗剂E21R和抗肿瘤坏死因子α单抗(Moab)CA2在体内抑制这些细胞因子对JMML细胞生长和体内扩散的影响。我们在这里展示了在没有外源生长因子的情况下，JMML细胞重新增殖到高水平。在移植时或移植后4周给予E21R可显著降低小鼠骨髓中的JMML细胞负荷。相反，单抗CA2本身没有作用，但与E21R在几乎消除小鼠骨髓中的JMML细胞方面有协同作用。在脾和外周血中，E21R对JMML细胞有清除作用，而单抗CA2则无此作用。重要的是，对同时植入来自正常捐赠者和JMML患者的细胞的小鼠的研究表明，E21R优先消除白血病细胞。这是首次在体内使用特定的GM-CSF抑制剂，结果表明GM-CSF在JMML的发病机制中发挥了重要作用。E21R可能为人类侵袭性白血病的治疗提供一种新的、特异的方法。
Granulocyte-macrophage colony-stimulating factor (GM-CSF ) and tumor necrosis factor alpha (TNFalpha) have been implicated in the pathogenesis of the fatal childhood disease termed juvenile myelomonocytic leukemia (JMML). We used a severe combined immunodeficient/nonobese diabetic (SCID/NOD) mouse model of JMML and examined the effect of inhibiting these cytokines in vivo with the human GM-CSF antagonist and apoptotic agent E21R and the anti-TNFalpha monoclonal antibody (MoAb) cA2 on JMML cell growth and dissemination in vivo. We show here that JMML cells repopulated to high levels in the absence of exogeneous growth factors. Administration of E21R at the time of transplantation or 4 weeks after profoundly reduced JMML cell load in the mouse bone marrow. In contrast, MoAb cA2 had no effect on its own, but synergized with E21R in virtually eliminating JMML cells from the mouse bone marrow. In the spleen and peripheral blood, E21R eliminated JMML cells, while MoAb cA2 had no effect. Importantly, studies of mice engrafted simultaneously with cells from both normal donors and from JMML patients showed that E21R preferentially eliminated leukemic cells. This is the first time a specific GM-CSF inhibitor has been used in vivo, and the results suggest that GM-CSF plays a major role in the pathogenesis of JMML. E21R might offer a novel and specific approach for the treatment of this aggressive leukemia in man.
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影响因子：
20.3
作者：
P. Emanuel;Lana J. Bates;R. Castleberry;R. Gualtieri;K. Zuckerman
通讯作者：
P. Emanuel;Lana J. Bates;R. Castleberry;R. Gualtieri;K. Zuckerman
粒细胞巨噬细胞集落刺激因子是幼年慢性粒细胞白血病细胞增殖的内源性调节因子。
影响因子：
20.3
作者：
Gualtieri,RJ;Emanuel,PD;Zuckerman,KS;Martin,G;Clark,SC;Shadduck,RK;Dracker,RA;Akabutu,J;Nitschke,R;Hetherington,ML
通讯作者：
Hetherington,ML
影响因子：
56.9
作者：
LICHTER, P;TANG, CJC;WARD, DC
通讯作者：
WARD, DC
同种异体骨髓移植治疗幼年型慢性粒细胞白血病儿童。
影响因子：
20.3
作者：
Sanders,JE;Buckner,CD;Thomas,ED;Fleischer,R;Sullivan,KM;Appelbaum,FA;Storb,R
通讯作者：
Storb,R