The Baxα:Bcl‐2 ratio modulates the response to dexamethasone in leukaemic cells and is highly variable in childhood acute leukaemia

The Baxα:Bcl‐2 ratio modulates the response to dexamethasone in leukaemic cells and is highly variable in childhood acute leukaemia
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Baxα:Bcl-2 比率调节白血病细胞对地塞米松的反应,并且在儿童急性白血病中变化很大

DOI:
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发表时间:
1997
影响因子:
6.4
通讯作者:
L. Smets
L. Smets
中科院分区:
医学1区
文献类型:
--
作者:
G. Salomons;H. Brady;M. Verwijs;J. D. van den Berg;A. Hart;H. van den Berg;H. Behrendt;K. Hahlen;L. Smets

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Bcl-2 过表达已被证明可以抑制多种刺激诱导的细胞凋亡,而 Baxα 相对于 Bcl-2 的优势会加速细胞凋亡刺激下的细胞凋亡。我们试图研究这些细胞凋亡调节基因产物与白血病的相关性。在一组白血病和淋巴瘤细胞系(HL60、DoHH2、CEM C7、L1210 和 S49)中,通过蛋白质印迹分析评估的 Baxα 与 Bcl-2 比率与对地塞米松治疗的敏感性相关。此外,在 HAbaxα 转染的 CEM C7 克隆中,发现地塞米松和毒胡萝卜素敏感性存在类似的相关性。在儿童急性淋巴细胞白血病或粒细胞白血病(ALL,n = 48;AML,n = 8)患者的骨髓抽吸物中,Bcl-2 和 Baxα 水平变化很大,但完全在 Baxα 转染子和已建立的细胞系中发现的范围内。 T 系 ALL 中的 Bcl-2 水平低于 B 系 ALL,这可能归因于 Bcl-2 和 WBC 之间同时存在负相关关系。相比之下,Baxα:Bcl-2 独立于任何表现特征,并且很大程度上依赖于 Baxα 水平。结果表明,Baxα:Bcl-2,而不是单独的 Bcl-2,对于白血病细胞系和 ALL 中药物诱导的细胞凋亡的存活很重要。国际。 J. Cancer 71: 959‐965, 1997。© 1997 Wiley‐Liss Inc.
Bcl‐2 over‐expression has been shown to inhibit apoptosis induced by a variety of stimuli, whereas a predominance of Baxα to Bcl‐2 accelerates apoptosis upon apoptotic stimuli. We sought to study the relevance of these apoptotic regulating gene products in leukaemia. In a panel of leukaemia and lymphoma cell lines (HL60, DoHH2, CEM C7, L1210 and S49), the Baxα‐to‐Bcl‐2 ratio as assessed by Western‐blot analysis correlated with sensitivity to dexamethasone treatment. In addition, in HAbaxα‐transfected CEM C7 clones, a similar correlation was found for dexamethasone and thapsigargin sensitivity. In bone‐marrow aspirates from patients with childhood acute lymphoblastic or myelocytic leukaemia (ALL, n = 48; AML, n = 8), the Bcl‐2 and Baxα levels were highly variable, but well within the range found in the Baxα transfectants and in the established cell lines. Bcl‐2 levels were lower in T‐ than in B‐lineage ALL, which could be ascribed to simultaneous inverse relation between Bcl‐2 and WBC. By contrast, Baxα:Bcl‐2 was independent of any presenting feature and was largely dependent on Baxα levels. Results suggest that Baxα:Bcl‐2, rather than Bcl‐2 alone is important for the survival of drug‐induced apoptosis in leukemic cell lines and ALL. Int. J. Cancer 71: 959‐965, 1997. © 1997 Wiley‐Liss Inc.
DOI: 10.1182/blood.v87.3.1155.bloodjournal8731155
发表时间: 1996-02-01
期刊: BLOOD
影响因子: 20.3
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DOI: --
发表时间: 1993
期刊: Blood
影响因子: 20.3
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DOI: --
发表时间: 1995
期刊: Blood
影响因子: 20.3
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DOI: 10.1159/000365550
发表时间: 2014-01-01
影响因子: 1.7
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