Granulocyte colony-stimulating factor activation of Stat3 alpha and Stat3 beta in immature normal and leukemic human myeloid cells
Granulocyte colony-stimulating factor activation of Stat3 alpha and Stat3 beta in immature normal and leukemic human myeloid cells
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DOI：
10.1182/blood.v88.7.2442.bloodjournal8872442
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发表时间：
1996-10-01
期刊：
影响因子：
20.3
通讯作者：
Tweardy, DJ
中科院分区：
文献类型：
--
作者：
Chakraborty, A;White, SM;Tweardy, DJ
粒细胞集落刺激因子（G-CSF）是指导中性粒细胞分化的关键细胞因子。急性髓性白血病（AML）细胞，经常来自这一谱系，通过增殖而不分化对G-CSF产生异常反应。这种异常反应的基础尚不清楚。在本研究中，我们研究了未成熟正常和白血病人髓细胞中G-CSF信号是否在信号转导和转录激活因子（STAT）蛋白的激活水平上发生分化。我们比较了在G-CSF刺激的未成熟正常和白血病人骨髓细胞中活化的STAT蛋白谱，G-CSF在除HL60外的所有AML细胞系和6个未培养AML患者样本中的3个中活化Stat3 α。在正常的人CD34（+）骨髓细胞和HL60细胞中，都报道了对G-CSF的分化反应，G-CSF不激活Stat3 α；相反，它只激活了一种83 kD的Stat3形式，该形式被证明是Stat3的一种短形式Stat3 β的人类同源物。由于Stat3 β的转录活性与Stat3 α不同，这些结果表明，骨髓细胞中两种Stat3亚型的平衡可能影响基因激活的细胞模式，从而影响这些细胞对G-CSF的分化能力。(C) 1996年由美国血液病学会出版。
Granulocyte colony-stimulating factor (G-CSF) is the cytokine critical for directing neutrophilic granulocyte differentiation. Acute myelogenous leukemia (AML) cells, which frequently arise from this lineage, respond aberrantly to G-CSF by proliferating without differentiating. The basis for this abnormal response is unknown. In the present study, we investigated whether G-CSF signaling in immature normal and leukemic human myeloid cells diverges at the level of activation of signal transducers and activators of transcription (STAT) proteins. We compared the profile of STAT proteins activated in G-CSF-stimulated immature normal and leukemic human myeloid cells, G-CSF activated Stat3 alpha in all AML cell lines examined except HL60 and in three of six uncultured AML patient samples, In normal human CD34(+) bone marrow cells and HL60 cells, both reported to differentiate in response to G-CSF, G-CSF did not activate Stat3 alpha; rather, it activated only an 83 kD form of Stat3 that proved to be the human homologue of a short form of Stat3, Stat3 beta. Because the transcriptional activity of Stat3 beta is distinct from Stat3 alpha, these results suggest that the balance of the two Stat3 isoforms in myeloid cells may influence the cellular pattern of gene activation and consequently the ability of these cells to differentiate in response to G-CSF. (C) 1996 by The American Society of Hematology.