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正常造血与血液系统恶性肿瘤:经典Wnt信号通路及基质微环境的作用

Normal hematopoiesis and hematologic malignancies: role of canonical Wnt signaling pathway and stromal microenvironment.

作者信息

Seke Etet Paul Faustin, Vecchio Lorella, Bogne Kamga Patrice, Nchiwan Nukenine Elias, Krampera Mauro, Nwabo Kamdje Armel Hervé

机构信息

Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah, 51452 Al-Qaseem, Saudi Arabia.

出版信息

Biochim Biophys Acta. 2013 Jan;1835(1):1-10. doi: 10.1016/j.bbcan.2012.08.002. Epub 2012 Sep 5.

Abstract

Wnts are a family of evolutionary-conserved secreted signaling molecules critically involved in a variety of developmental processes and in cell fate determination. A growing body of evidence suggests that Wnt signaling plays a crucial role in the influence of bone marrow stromal microenvironment on the balance between hematopoietic stem cell self-renewal and differentiation. Emerging clinical and experimental evidence also indicates Wnt signaling involvement in the disruption of the latter balance in hematologic malignancies, where the stromal microenvironment favors the homing of cancer cells to the bone marrow, as well as leukemia stem cell development and chemoresistance. In the present review, we summarize and discuss the role of the canonical Wnt signaling pathway in normal hematopoiesis and hematologic malignancies, with regard to recent findings on the stromal microenvironment involvement in these process and diseases.

摘要

Wnt 是一族进化保守的分泌型信号分子,在多种发育过程以及细胞命运决定中起关键作用。越来越多的证据表明,Wnt 信号传导在骨髓基质微环境对造血干细胞自我更新与分化平衡的影响中发挥着关键作用。新出现的临床和实验证据还表明,Wnt 信号传导参与了血液系统恶性肿瘤中上述平衡的破坏,在这类肿瘤中,基质微环境有利于癌细胞归巢至骨髓,以及白血病干细胞的发育和化疗耐药。在本综述中,我们总结并讨论了经典 Wnt 信号通路在正常造血和血液系统恶性肿瘤中的作用,涉及基质微环境参与这些过程和疾病的最新研究发现。

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