Journal Article

TGF-β1-induced PI3K/Akt/NF-κB/MMP9 signalling pathway is activated in Philadelphia chromosome-positive chronic myeloid leukaemia hemangioblasts

Xishan Zhu, Liang Wang, Bin Zhang, Jing Li, Xiaowei Dou and Robert Chunhua Zhao

in The Journal of Biochemistry

Published on behalf of The Japanese Biochemical Society

Volume 149, issue 4, pages 405-414
Published in print April 2011 | ISSN: 0021-924X
Published online February 2011 | e-ISSN: 1756-2651 | DOI: https://dx.doi.org/10.1093/jb/mvr016
TGF-β1-induced PI3K/Akt/NF-κB/MMP9 signalling pathway is activated in Philadelphia chromosome-positive chronic myeloid leukaemia hemangioblasts

Show Summary Details

Preview

Overwhelming evidence from chronic myeloid leukaemia (CML) research indicates that patients harbour quiescent CML stem cells that are responsible for blast crisis. While the haematopoietic stem cell (HSC) origin of CML was first suggested over 30 years ago, recently CML-initiating cells beyond HSCs are also being investigated. We have previously isolated fetal liver kinase-1-positive (Flk1+) cells carrying the BCR/ABL fusion gene from the bone marrow of Philadelphia chromosome-positive (Ph+) patients with hemangioblast property. Here, we show that these cells behave abnormally comparing with the hemangioblasts in healthy donors. These Ph+ putative CML hemangioblast up-regulated TGF-β1 and result in activating matrix metalloproteinase-9 to enhance s-KitL and s-ICAM-1 secretion. Further studies showed that phosphatidylinositol-3 kinase (PI3K)/Akt/nuclear factor-κB signalling pathway was involved in CML pathogenesis. These findings provide direct evidence for the first time that hemangioblasts beyond HSCs play a critical role in the progression of CML.

Keywords: chronic myeloid leukaemia (CML); hemangioblasts; Hematopoietic Stem Cell (HSC); Matrix Metalloproteinase-9 (MMP-9); transforming growth factor-beta 1(TGF-β1)

Journal Article.  5363 words.  Illustrated.

Subjects: Biochemistry

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content. subscribe or login to access all content.