title: Molecular biological characteristics of the recruitment of hematopoietic stem cells from bone marrow niche in chronic myeloid leukemia.
abstract: 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-β1, 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-β1. Besides, phosphatidylinositol-3 kinase (PI3K)/Akt/nuclear factor (NF)-κB signaling pathway was evidenced to govern this stem cell recruitment in CML pathogenesis. Overall, our observations defined a novel critical role for TGF-β1 induced PI3K/Akt/NF-κB 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-κB signaling pathway.
authors.affiliation: Department of Core Laboratory Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital Sichuan, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Department of Core Laboratory Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital Sichuan, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Core Laboratory Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital Sichuan, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Core Laboratory Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital Sichuan, China.
authors.forename: Chenglong
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Core Laboratory Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital Sichuan, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D047468:Immunoprecipitation; D017404:In Situ Hybridization, Fluorescence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D055153:Stem Cell Niche; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D055815:Young Adult
chemical_list: D016328:NF-kappa B; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Chronic myeloid leukemia (CML); TGF-β1; hematopoietic stem cell (HSC); matrix metalloproteinase-9 (MMP-9); mesenchymal stem cell (MSC); s-ICAM-1; s-KitL