High IGFBP-3 levels in marrow plasma in early-stage MDS: effects on apoptosis and hemopoiesis

Wilson, Heather M.; Lesnikov, Vladimir; Plymate, Stephen R.; Ward, Jessica; Deeg, H. Joachim

doi:10.1038/sj.leu.2403672

Cited by 9 publications

(5 citation statements)

References 40 publications

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“…function either as an antiapoptotic or proapoptotic factor depending on the cell type and condition (Granata et al, 2004). Wilson et al (2005) has reported that IGFBP3 may protect myeloid cells against apoptosis mediated by Fas ligand or tumor necrosis factor alpha (TNF␣). Accordingly, IGFBP3 could protect macrophage-like cells from apoptosis.…”

Section: Discussionmentioning

confidence: 99%

SARS spike protein induces phenotypic conversion of human B cells to macrophage-like cells

Chiang

Lin

Chow

et al. 2010

Molecular Immunology

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Massive aggregations of macrophages are frequently detected in afflicted lungs of patients with severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infection. In vitro, ectopic expression of transcription factors, in particular CCAAT/enhancer-binding protein alpha (C/EBPα) and C/EBPβ, can convert B cells into functional macrophages. However, little is known about the specific ligands responsible for such phenotype conversion. Here, we investigated whether spike protein of SARS-CoV can act as a ligand to trigger the conversion of B cells to macrophages. We transduced SARS-CoV spike protein-displayed recombinant baculovirus (SSDRB), vAtEpGS688, into peripheral B cells and B lymphoma cells. Cell surface expression of CD19 or Mac-1 (CD11b) was determined by flow cytometry. SSDRB-mediated changes in gene expression profiles of B lymphoma cells were analyzed by microarray. In this report, we showed that spike protein of SARS virus could induce phenotypic conversion of human B cells, either from peripheral blood or B lymphoma cells, to macrophage-like cells that were steadily losing the B-cell marker CD19 and in turn expressing the macrophage-specific marker Mac-1. Furthermore, we found that SSDRB enhanced the expression of CD86, hypoxia-inducible factor-1α (HIF1α), suppressor of cytokine signaling (SOCS or STAT-induced STAT inhibitor)-3, C/EBPβ, insulin-like growth factor-binding protein 3 (IGFBP3), Krüpple-like factor (KLF)-5, and CD54, without marked influence on C/EBPα or PU.1 expression in transduced cells. Prolonged exposure to hypoxia could also induce macrophage-like conversion of B cells. These macrophage-like cells were defective in phagocytosis of red fluorescent beads. In conclusion, our results suggest that conversion of B cells to macrophage-like cells, similar to a pathophysiological response, could be mediated by a devastating viral ligand, in particular spike protein of SARS virus, or in combination with severe local hypoxia, which is a condition often observed in afflicted lungs of SARS patients.

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Section: Discussionmentioning

confidence: 99%

SARS spike protein induces phenotypic conversion of human B cells to macrophage-like cells

Chiang

Lin

Chow

et al. 2010

Molecular Immunology

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“…It has been suggested that IGFBPs are involved in the regulation of pro‐B cell development as well as regulation and proliferation of T cells [48, 49]. Furthermore, IGFBP‐3 has been suggested to promote proliferation of primitive HPC in vitro, whereas other authors did not observe an effect of IGFBP‐3 on GFU‐GM or BFU‐E [50, 51]. We have demonstrated that IGFBP‐1, IGFBP‐2, and IGFBP‐3 had no effect on proliferation or maintenance of a primitive immunophenotype in culture medium without cellular support.…”

Section: Discussionmentioning

confidence: 99%

Molecular and Secretory Profiles of Human Mesenchymal Stromal Cells and Their Abilities to Maintain Primitive Hematopoietic Progenitors

et al. 2007

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Mesenchymal stromal cells (MSC) provide a supportive cellular microenvironment and are able to maintain the self-renewal capacity of hematopoietic progenitor cells (HPC). Isolation procedures for MSC vary extensively, and this may influence their biologic properties. In this study, we have compared human MSC isolated from bone marrow (BM) using two culture conditions, from cord blood (CB), and from adipose tissue (AT). The ability to maintain long-term cultureinitiating cell frequency and a primitive CD34 ؉ CD38؊ immunophenotype was significantly higher for MSC derived from BM and CB compared with those from AT. These results were in line with a significantly higher adhesion of HPC to MSC from BM and CB versus MSC from AT. We have compared the cytokine production of MSC by cytokine antibody arrays, enzyme-linked immunosorbent assay, and a cytometric bead array. There were reproducible differences in the chemokine secretion profiles of various MSC preparations, but there was no clear concordance with differences in their potential to maintain primitive function of HPC. Global gene expression profiles of MSC preparations were analyzed and showed that adhesion proteins including cadherin-11, N-cadherin, vascular cell adhesion molecule 1, neural cell adhesion molecule 1, and integrins were highly expressed in MSC preparations derived from BM and CB. Thus, MSC from BM and CB are superior to MSC from AT for maintenance of primitive HPC. The latter property is associated with specific molecular profiles indicating the significance of cell-cell junctions but not with secretory profiles.

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“…Early stages of MDS display an increased apoptosis, contributing to ineffective hematopoiesis and peripheral cytopenia. Increased levels of tumor necrosis factor (TNF)a, 34 as well as the insulin-like growth factor-binding protein 3 (IGFBP-3), 35 has been observed and could be responsible for augmented TNFamediated apoptosis. Conversely, later stages of MDS present an excessive survival and leukemic evolution of MDS arises through lesions that inhibit apoptotic control mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Frequent elevation of Akt kinase phosphorylation in blood marrow and peripheral blood mononuclear cells from high-risk myelodysplastic syndrome patients

et al. 2005

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The serine/threonine kinase Akt, a downstream effector of phosphatidylinositol 3-kinase (PI3K), is known to play an important role in antiapoptotic signaling and has been implicated in the aggressiveness of a number of different human cancers including acute myeloid leukemia (AML). The progression of myelodysplastic syndromes (MDSs) to AML is thought to be associated with abrogation of apoptotic control mechanisms. However, little is known about signal transduction pathways which may be involved in enhanced survival of MDS cells. In this report, we have performed immunocytochemical and flow cytometric analysis to evaluate the levels of activated Akt in bone marrow or peripheral blood mononuclear cells from patients diagnosed with MDS. We observed high levels of Ser473 phosphorylated Akt (p-Akt) staining in 90% of the cases (n ¼ 22) diagnosed as high-risk MDS, whereas mononuclear cells from normal bone marrow or low-risk MDS patients showed low or absent Ser473 p-Akt staining. Furthermore, all high-risk MDS patients also demonstrated high expression of the Class I PI3K p110d catalytic subunit and a decreased expression of PTEN. Taken together, our results suggest that Akt activation might be one of the factors contributing to the decreased apoptosis rate observed in patients with high-risk MDS.

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High IGFBP-3 levels in marrow plasma in early-stage MDS: effects on apoptosis and hemopoiesis

Cited by 9 publications

References 40 publications

SARS spike protein induces phenotypic conversion of human B cells to macrophage-like cells

SARS spike protein induces phenotypic conversion of human B cells to macrophage-like cells

Molecular and Secretory Profiles of Human Mesenchymal Stromal Cells and Their Abilities to Maintain Primitive Hematopoietic Progenitors

Frequent elevation of Akt kinase phosphorylation in blood marrow and peripheral blood mononuclear cells from high-risk myelodysplastic syndrome patients

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