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[多种造血生长因子对急性髓性白血病原始细胞的作用]

[Activity of various hematopoietic growth factors on acute myeloblastic leukemia blasts].

作者信息

Almeida J, del Cañizo M C, Vidriales B, Hernández M D, Galende J, San Miguel J

机构信息

Servicio de Hematología, Hospital Universitario de Salamanca.

出版信息

Sangre (Barc). 1996 Feb;41(1):3-8.

PMID:8779032
Abstract

PURPOSE

Acute myeloblastic leukaemia (AML) cells respond to some extent to the action of haemopoietic growth factors (HGF). This work is aimed to analyse the effect of IL-3, GM-CSF and G-CSF on the proliferative and self-replication capabilities of AML cells and to correlate such response with the morphological and immunological characteristics of the blast cells.

PATIENTS AND METHODS

Mononucleated cells from the peripheral blood of 26 AML patients were incubated in liquid medium without serum in presence of IL-3 and GM-CSF alone and in combination with G-CSF. Cell proliferation was evaluated by determination of the increase in the number of cells harvested after incubation with the HGF. The proliferative response was studied in 8 cases by flow cytometry analysis of the cell cycle (number of cells in S-phase). The capability of IL-3 and GM-CSF to induce self-replication of the leukaemic clonogenic cell (CFU-L) was analysed in 9 cases by techniques of replanting on semi-solid medium.

RESULTS

Cell proliferation was induced with IL-3 in more cases than with GM-CSF (50% vs 28%); furthermore, the stimulus induced by IL-3 was also more evident, as the number of cells harvested was greater than that corresponding to GM-CSF (2.1 +/- 1.1 x 10(6) cell/mL vs 1.4 +/- 1.4 x 10(6) cells/mL, p = 0.10). Although no clear correlation was seen between the proliferative response to HGF and the immunologic or morphologic subtype of the blast cells, no response to GM-CSF was detected in those cases classified as M2 nor in the CD15-positive leukaemias. A synergistic effect of G-CSF and IL-3 or GM-CSF was found in only 20% of the cases. Both IL-3 and GM-CSF augmented the number of cells in S phase in all the cases analysed; this increase was higher in M1 and M2 with respect to the leukaemias with monocytic component.

CONCLUSIONS

IL-3 and GM-CSF induced self-replication of CFU-L in a half of the cases. This effect was not dependent upon the kind of stimulating agent used (IL-3 or GM-CSF), and appeared unrelated to the morphologic or immunologic characteristics of the leukaemia.

摘要

目的

急性髓系白血病(AML)细胞在一定程度上对造血生长因子(HGF)的作用有反应。本研究旨在分析白细胞介素-3(IL-3)、粒细胞-巨噬细胞集落刺激因子(GM-CSF)和粒细胞集落刺激因子(G-CSF)对AML细胞增殖和自我复制能力的影响,并将这种反应与原始细胞的形态和免疫特征相关联。

患者和方法

将26例AML患者外周血中的单核细胞在无血清的液体培养基中培养,分别加入单独的IL-3、GM-CSF以及与G-CSF联合使用。通过测定与HGF孵育后收获的细胞数量增加来评估细胞增殖。通过细胞周期的流式细胞术分析(S期细胞数量)对8例患者的增殖反应进行研究。通过在半固体培养基上重新种植的技术,对9例患者分析IL-3和GM-CSF诱导白血病克隆形成细胞(CFU-L)自我复制的能力。

结果

与GM-CSF相比,更多病例中IL-3诱导了细胞增殖(50%对28%);此外,IL-3诱导的刺激也更明显,因为收获的细胞数量大于GM-CSF对应的数量(2.1±1.1×10⁶个细胞/毫升对1.4±1.4×10⁶个细胞/毫升,p = 0.10)。虽然对HGF的增殖反应与原始细胞的免疫或形态亚型之间未发现明显相关性,但在分类为M2的病例或CD15阳性白血病中未检测到对GM-CSF的反应。仅在20%的病例中发现G-CSF与IL-3或GM-CSF有协同作用。在所有分析的病例中,IL-3和GM-CSF均增加了S期细胞的数量;相对于有单核细胞成分的白血病,M1和M2中的这种增加更高。

结论

IL-3和GM-CSF在一半的病例中诱导了CFU-L的自我复制。这种效应不依赖于所用刺激剂的类型(IL-3或GM-CSF),且似乎与白血病的形态或免疫特征无关。

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