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重组人粒细胞集落刺激因子和粒细胞-单核细胞集落刺激因子对骨髓增生异常综合征体外造血的影响。

Effects of recombinant human granulocyte colony stimulating factor and granulocyte-monocyte colony stimulating factor on in vitro hemopoiesis in the myelodysplastic syndromes.

作者信息

Nagler A, Ginzton N, Negrin R, Bang D, Donlon T, Greenberg P

机构信息

Department of Medicine, Stanford University Medical Center, California.

出版信息

Leukemia. 1990 Mar;4(3):193-202.

PMID:1690318
Abstract

We evaluated the effects of recombinant human granulocyte colony stimulating factor (rhG-CSF) and granulocyte-monocyte colony stimulating factor (rhGM-CSF) on the in vitro proliferative, differentiative, and regenerative responsiveness of marrow cells from myelodysplastic syndrome patients (MDS) in comparison to those from normal individuals. Our studies showed decreased primary clonogenicity of myeloid (CFU-GM) and erythroid (BFU-E) hemopoietic progenitor cells from the MDS patients. rhGM-CSF had more potent stimulatory effects than rhG-CSF for MDS marrow CFU-GM growth; no enhanced cellular proliferation in the MDS patients was observed in liquid culture with either rhGM-CSF or rhG-CSF. Decreased myeloid clonal cell self-generation and/or recruitment occurred in the MDS patients upon exposure to either rhG-CSF or rhGM-CSF. rhG-CSF demonstrated more potent granulocytic differentiation effects than rhGM-CSF both for normals and MDS patients using marrow enriched for immature myeloid cells with lesser differentiation noted for MDS. Cytogenetic abnormalities, present with or without additional normal karyotypes in native marrow of four MDS patients, persisted after culture with rhG-CSF, indicating induced differentiation of both normal and abnormal clones. Although proliferative and differentiative effects were seen with both factors these data show MDS marrow cells in vitro to have predominantly differentiative responsiveness to rhG-CSF and proliferative responsiveness to rhGM-CSF.

摘要

我们评估了重组人粒细胞集落刺激因子(rhG-CSF)和粒细胞-单核细胞集落刺激因子(rhGM-CSF)对骨髓增生异常综合征患者(MDS)骨髓细胞体外增殖、分化及再生反应的影响,并与正常个体的骨髓细胞进行了比较。我们的研究表明,MDS患者的髓系(CFU-GM)和红系(BFU-E)造血祖细胞的原始克隆形成能力下降。rhGM-CSF对MDS患者骨髓CFU-GM生长的刺激作用比rhG-CSF更强;在rhGM-CSF或rhG-CSF液体培养中,未观察到MDS患者细胞增殖增强。MDS患者在接触rhG-CSF或rhGM-CSF后,髓系克隆细胞自我生成和/或募集减少。使用富含未成熟髓系细胞的骨髓,rhG-CSF对正常人和MDS患者的粒细胞分化作用均比rhGM-CSF更强,MDS患者的分化作用较弱。4例MDS患者的原始骨髓中存在细胞遗传学异常,无论是否伴有额外的正常核型,在rhG-CSF培养后仍持续存在,表明正常克隆和异常克隆均发生了诱导分化。尽管两种因子都有增殖和分化作用,但这些数据表明,MDS骨髓细胞在体外对rhG-CSF主要表现为分化反应,对rhGM-CSF主要表现为增殖反应。

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