Deregulated expression of Kruppel-like factors in acute myeloid leukemia
Deregulated expression of Kruppel-like factors in acute myeloid leukemia
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DOI：
10.1016/j.leukres.2011.03.010
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发表时间：
2011-07-01
影响因子：
2.7
通讯作者：
Tschan, Mario P.
中科院分区：
文献类型：
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作者：
Humbert, Magali;Halter, Veronika;Tschan, Mario P.
已知 Kruppel 样转录因子 (KLF) 参与细胞分化，促使我们研究它们在急性髓系白血病 (AML) 母细胞中的表达，这些细胞的分化通常受到阻碍。我们确定了在大量原发性 AML 患者样本、来自健康供体的 CD34(+) 祖细胞和粒细胞中具有推定作用的 KLF 的表达模式。我们发现与正常粒细胞相比，KLF2、KLF3、KLF5 和 KLF6 在 AML 母细胞和 CD34(+) 祖细胞中的表达显着降低。此外，我们发现接受口服 ATRA 的急性早幼粒细胞白血病患者 KLF 水平显着升高。因此，我们在 NB4 和 HT93 APL 中观察到 ATRA 处理后 KLF5/6 的强烈诱导，但在 ATRA 抗性 NB4-R 细胞中没有观察到。最后，敲除 NB4 细胞中的 KLF5 或 KLF6 会显着减弱中性粒细胞的分化。总之，我们发现与成熟中性粒细胞相比，原发性 AML 样本中 KLF 转录因子受到显着抑制，并进一步表明 KLF5 和 KLF6 在功能上参与 APL 细胞的中性粒细胞分化。 (C) 2011 Elsevier Ltd. 保留所有权利。
The known participation of Kruppel-like transcription factors (KLF) in cellular differentiation prompted us to investigate their expression in acute myeloid leukemia (AML) blast cells that are typically blocked in their differentiation. We determined the expression patterns of KLFs with a putative role in myeloid differentiation in a large cohort of primary AML patient samples, CD34(+) progenitor cells and granulocytes from healthy donors. We found that KLF2, KLF3, KLF5 and KLF6 are significantly lower expressed in AML blast and CD34(+) progenitor cells as compared to normal granulocytes. Moreover, we found markedly increased KLF levels in acute promyelocytic leukemia patients who received oral ATRA. Accordingly, we observed a strong induction of KLF5/6 upon ATRA-treatment in NB4 and HT93 APL but not in ATRA-resistant NB4-R cells. Lastly, knocking down KLF5 or KLF6 in NB4 cells significantly attenuated neutrophil differentiation. In conclusion, we found a significant repression of KLF transcription factors in primary AML samples as compared to mature neutrophils and further show that KLF5 and KLF6 are functionally involved in neutrophil differentiation of APL cells. (C) 2011 Elsevier Ltd. All rights reserved.