Impaired clonogenic growth of myelodysplastic bone marrow progenitors in vitro is irrelevant to their apoptotic state

Michalopoulou, Sotiria; Micheva, Ilina; Kouraklis-Symeonidis, Alexandra; Kakagianni, Theodora; Symeonidis, Argiris; Zoumbos, Nicholas

doi:10.1016/j.leukres.2003.12.004

Cited by 12 publications

(8 citation statements)

References 39 publications

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“…We found that apoptosis of BM CD34 + cells in the patients, as detected by Annexin-V, was increased but, interestingly, the survival and growth of CD34 + progenitors in the culture was not correlated to the degree of apoptosis. Consistent with this, we have recently shown that apoptosis does not account for the impaired clonogenicity of haematopoietic progenitors, as non-apoptotic as well as apoptotic bone marrow CD34 + cells exhibited similar growth in a system of short-term semisolid culture (Michalopoulou et al, 2004). Accordingly, the capacity of CD34 + cells to generate DCs, as our experiments have shown, did not differ when apoptotic and non-apoptotic CD34 + cells were separately cultured (data not shown).…”

Section: Discussionsupporting

confidence: 89%

Impaired generation of bone marrow CD34‐derived dendritic cells with low peripheral blood subsets in patients with myelodysplastic syndrome

et al. 2004

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SummaryMyelodysplastic syndrome (MDS) is a stem cell disorder characterized by ineffective haematopoiesis and blood cytopenias. The present study investigated the potential of bone marrow CD34 + progenitors in MDS patients to proliferate and differentiate into dendritic cells (DCs) in a cytokine-supplemented liquid culture system and analysed the status of blood DC subsets in these patients. CD34 + progenitors had low potential to generate DCs in vitro, as the number of DCs obtained from one CD34 + cell was significantly lower compared with controls (median value 0AE2 vs. 4, P ¼ 0AE003). In patients, the survival and proliferation of CD34 + cells in culture was not correlated to the degree of apoptosis. Phenotypically and functionally CD34 + -derived DCs were similar in MDS patients and normal subjects. The percentage of both circulating DC subsets in patients was extremely diminished compared with controls (myeloid DC: 0AE10 ± 0AE10% vs. 0AE35 ± 0AE13%, P < 0AE001; plasmacytoid DC: 0AE11 ± 0AE10% vs. 0AE37 ± 0AE14%, P < 0AE001). In cases with the 5q deletion both CD34-derived DCs and blood DCs harboured the cytogenetic abnormality. Our results indicate that, in MDS, the production of DCs is affected by the neoplastic process resulting in ineffective 'dendritopoiesis' with low blood DC precursor numbers. This quantitative DC defect probably contributes to the poor immune response against infectious agents and to the escape of the malignant clone from immune recognition with disease progression towards acute leukaemia.

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Section: Discussionsupporting

confidence: 89%

Impaired generation of bone marrow CD34‐derived dendritic cells with low peripheral blood subsets in patients with myelodysplastic syndrome

et al. 2004

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“…Cell colonies were counted in an inverted microscope (Olympus) 10–14 days after the plating. Aggregates of >20 cells were considered as colonies [35, 36]. …”

Section: Methodsmentioning

confidence: 99%

Oxidative stress due to radiation in CD34+ Hematopoietic progenitor cells: protection by IGF-1

Floratou

Giannopoulou

Antonacopoulou

et al. 2012

Journal of Radiation Research

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Radiation exerts direct as well as indirect effects on DNA through the generation of reactive oxygen species (ROS). Irradiated hematopoietic progenitor cells (HPCs) experience DNA strand breaks, favoring genetic instability, due to ROS generation. Our aim was to study the effect of a range of radiation doses in HPCs and the possible protective mechanisms activated by insulin-like growth factor-1 (IGF-1). ROS generation was evaluated, in the presence or absence of IGF-1 in liquid cultures of human HPCs-CD34+ irradiated with 1-, 2- and 5-Gy X-rays, using a flow cytometry assay. Manganese superoxide dismutase (MnSOD) expression was studied by western blot analysis and visualized by an immunofluorescence assay. Apoptosis was estimated using the following assays: Annexin-V assay, DNA degradation assay, BCL-2/BAX mRNA and protein levels and caspase-9 protein immunofluorescence visualization. Viability and clonogenic potential were studied in irradiated HPCs. The generation of superoxide anion radicals at an early and a late time point was increased, while the hydrogen peroxide generation at a late time point was stable. IGF-1 presence further enhanced the radiation-induced increase of MnSOD at 24 h post irradiation. IGF-1 inhibited the mitochondria-mediated pathway of apoptosis by regulating the m-RNA and protein expression of BAX, BCL-2 and the BCL-2/BAX ratio and by decreasing caspase-9 protein expression. IGF-1 presence in culture media of irradiated cells restored the clonogenic capacity and the viability of HPCs as well. In conclusion, IGF-1 protects HPCs-CD34+ from radiation effects, by eliminating the oxidative microenvironment through the enhancement of MnSOD activation and by regulating the mitochondria-mediated pathway of apoptosis.

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“…A possible explanation for the survival of trisomy 8 cells despite an apparently specific immune attack and the induction of apoptosis was suggested by experiments demonstrating that annexin ϩ BM cells from MDS showed good hematopoietic colony formation. 5 Survival of abnormal CD34 cells in MDS might therefore be explicable based on apoptosis that is incomplete, as, for example, due to failure of signal transduction upstream of caspase 3 activation and the phosphatydyinositol membrane changes that result in annexin binding. 6,7 Previously we demonstrated on microarray analysis that proteins affecting apoptosis and proliferation, c-myc and CD1, were up-regulated in CD34 cells of patients with trisomy 8.…”

Section: Introductionmentioning

confidence: 99%

CD34 cells from patients with trisomy 8 myelodysplastic syndrome (MDS) express early apoptotic markers but avoid programmed cell death by up-regulation of antiapoptotic proteins

Sloand

Pfannes

Chen

et al. 2006

Blood

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Impaired clonogenic growth of myelodysplastic bone marrow progenitors in vitro is irrelevant to their apoptotic state

Cited by 12 publications

References 39 publications

Impaired generation of bone marrow CD34‐derived dendritic cells with low peripheral blood subsets in patients with myelodysplastic syndrome

Impaired generation of bone marrow CD34‐derived dendritic cells with low peripheral blood subsets in patients with myelodysplastic syndrome

Oxidative stress due to radiation in CD34+ Hematopoietic progenitor cells: protection by IGF-1

CD34 cells from patients with trisomy 8 myelodysplastic syndrome (MDS) express early apoptotic markers but avoid programmed cell death by up-regulation of antiapoptotic proteins

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