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Molecular biological characteristics of the recruitment of hematopoietic stem
cells from bone marrow niche in chronic myeloid leukemia
#MMPMID26722450
Zhu B
; Zhang J
; Chen J
; Li C
; Wang X
Int J Clin Exp Pathol
2015[]; 8
(10
): 12595-607
PMID26722450
show ga
Chronic myeloid leukemia (CML) can be contextualized as a disease of unregulated
self-renewal of stem cells which exist in a quiescent state and are instructed to
differentiate and mobilize to circulation under pathologic circumstances leading
to tumor invasion and metastasis. Here we found that matrix metalloproteinase-9
(MMP-9), induced by TGF-?1, upregulated s-KitL and s-ICAM-1, permitting the
transfer of c-kit(+) hematopoietic stem cells (HSCs) from the quiescent to
proliferative niche in CML. Further study showed that this MMP-9 production was
raised by CML specific BCR/ABL(+) oncogene mediated TGF-?1. Besides,
phosphatidylinositol-3 kinase (PI3K)/Akt/nuclear factor (NF)-?B signaling pathway
was evidenced to govern this stem cell recruitment in CML pathogenesis. Overall,
our observations defined a novel critical role for TGF-?1 induced PI3K/Akt/NF-?B
signaling pathway in the recruitment of the malignant cells in CML by releasing
s-KitL and s-ICAM-1 and this was through a distinct PI3K/Akt/NF-?B signaling
pathway.
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