Role of the STAT1 pathway in apoptosis induced by fludarabine and JAK kinase inhibitors in B-cell chronic lymphocytic leukemia
Role of the STAT1 pathway in apoptosis induced by fludarabine and JAK kinase inhibitors in B-cell chronic lymphocytic leukemia
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DOI：
10.1080/10428190400018398
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发表时间：
2005-03-01
影响因子：
2.6
通讯作者：
Juarez, C
中科院分区：
文献类型：
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作者：
Martinez-Lostao, L;Briones, J;Juarez, C
信号转导子和转录激活子 (STAT) 蛋白包含一系列与肿瘤转化有关的转录因子家族，尤其是血液恶性肿瘤。因此，JAK/STAT 通路作为这些肿瘤的治疗靶点很有吸引力。在本研究中，我们分析了氟达拉滨和两种 JAK 激酶抑制剂 AG490 和 WHI-P131 阻断 STAT1 激活并诱导 B 细胞慢性淋巴细胞白血病 (B-CLL) 细胞凋亡的能力。所有药物都能诱导所有研究患者的 B-CLL 细胞发生高比例的细胞凋亡。然而，只有 AG490 和 WHI-P131 能够强烈抑制 B-CLL 细胞的 STAT1 激活。总之，我们的数据表明 JAK 激酶抑制剂，例如 AG490 和 WHI-P131 能够抑制 B-CLL 细胞上的 STAT1 通路，并且是这些细胞凋亡的强诱导剂。
Signal transducers and activators of transcription ( STAT) proteins comprise a family of transcription factors that have been implicated in tumoral transformation, especially in hematological malignancies. Because of this, the JAK/STAT pathway is attractive as a therapeutic target in these tumors. In the present study, we analyzed the ability of fludarabine and two JAK kinase inhibitors, AG490 and WHI-P131, to block STAT1 activation and induce apoptosis on B-cell chronic lymphocytic leukemia (B-CLL) cells. All drugs were able to induce a high percentage of apoptosis on B-CLL cells from all patients studied. However, only AG490 and WHI-P131 were able to strongly suppress the STAT1 activation of B-CLL cells. In conclusion, our data show that JAK kinase inhibitors, such as AG490 and WHI-P131 are able to inhibit the STAT1 pathway on B-CLL cells and are strong inductors of apoptosis on these cells.