Targeting chronic myeloid leukemia stem cells: can transcriptional program be a druggable target for cancers?
Targeting chronic myeloid leukemia stem cells: can transcriptional program be a druggable target for cancers?
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DOI：
10.21037/sci.2018.03.05
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发表时间：
2018-01-01
影响因子：
--
通讯作者：
Kurokawa, Mineo
中科院分区：
文献类型：
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作者：
Masamoto, Yosuke;Kurokawa, Mineo
慢性粒细胞白血病（CML）是一种骨髓增生性肿瘤，由造血干细胞（HSC）中获得组成型活性BCR-ABL蛋白酪氨酸激酶引起。虽然酪氨酸激酶抑制剂（TKI）已将致命性疾病变为可控制的疾病，但由于TKI耐药白血病干细胞（LSC）的持续存在，大多数患者无法停止TKI治疗。已经做出了很多努力来找出在LSC中特异性地操作以选择性地靶向LSC的因子或途径，至少在临床前模型中具有一些有希望的结果。在本文中，我们简要回顾了Wnt/β-连环蛋白信号传导及其相关因子在CML LSC中的作用，特别关注Wnt/β-连环蛋白途径的主要效应子Tcf 1/Lef 1转录因子，最近发现该转录程序可被前列腺素E1靶向。
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm resulting from acquisition of constitutively active BCR-ABL protein tyrosine kinase in a hematopoietic stem cell (HSC). Though tyrosine kinase inhibitors (TKIs) have changed a fatal disease into manageable disease, most patients cannot discontinue TKI treatment due to persistence of TKI-resistant leukemia stem cells (LSCs). Much effort has been made to find out factors or pathways specifically operating in LSCs to selectively target LSCs, with some promising results at least in preclinical models. In this article, we briefly review the role of Wnt/beta-catenin signaling and its related factors in CML LSCs, especially focusing on Tcf1/Lef1 transcription factors, major effectors of Wnt/beta-catenin pathway, of which transcriptional program have recently been shown to be targetable with prostaglandin E1.