scholarly journals Difference in glycerol levels between leukemia and normal bone marrow stem cells

2014 ◽  
Vol 8 (1) ◽  
pp. 169-174 ◽  
Author(s):  
YING-SONG QIN ◽  
DAN-XIA BU ◽  
YING-YING CUI ◽  
XIANG-YU ZHANG
Author(s):  
Paula Laranjeira ◽  
Andreia Ribeiro ◽  
Sandrine Mendes ◽  
Ana Henriques ◽  
M. Luisa ◽  
...  

Stem Cells ◽  
1996 ◽  
Vol 14 (5) ◽  
pp. 533-547 ◽  
Author(s):  
Margaret E. Ruiz ◽  
John Freeman ◽  
John D. Bouhasin ◽  
Alan P. Knutsen ◽  
Mary J. C. Hendrix

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4430-4430
Author(s):  
Farzaneh Ashrafi ◽  
Fatemeh Nadali ◽  
Ardeshir Ghavamzadeh ◽  
Kamran Alimoghaddam ◽  
Shahrbano Rostami ◽  
...  

Abstract Abstract 4430 Background Nucleostemin (NS), a novel p53-binding protein has been shown essential for stem and cancer cell proliferation and implicated in oncogenesis. Nucleostemin expression had been shown in gastric cancer (SGC-7901) cells, human hepatocarcinoma (HepG2) cells, human cervical cancer (Hela) cells, human osteosarcoma (OS-732) cells. Aim This work designed to study the NS gene expression in bone marrow cells in acute promyelocytic leukemia (APL) patients and in normal bone marrow specimens. Materials &Methods We examined NS gene expression by Quantitative Real Time PCR in bone marrow specimens of 15 cases of APL patients, before treatment and in 4 bone marrow specimens of healthy donors of bone marrow transplantation. In the same samples of bone marrow aspiration morphology of smears was evaluated. Diagnosis of APL was based on morphology and positive PML/RARA in PCR. RT-PCR used to amplify the NS mRNA, and the GAPDH primer sets used for normalizing. For comparison of NS gene expreesion in 2 groups Mann-Whitney U test was used. Results 15 patients enrolled in this study, 11(73%) newly diagnosed APL and 4(27%) relapsed cases. Mean age of patients was 28.67±9.56 year. NS gene expressed in all bone marrow samples of APL patients. NS gene expressed in normal bone marrow specimens too. NS gene expression in bone marrow of APL patients was significantly higher than normal bone marrows(p value =0.002) Fig 1. There was no significant difference in NS gene expression between newly diagnosed and relapsed APL cases. Discussion According to the results of this study it seems that NS gene expressed in normal marrow. NS expression in adult bone marrow hematopoietic stem cells had been reported in previous reports and it had been shown that NS does not express in granulocytes and B lymphocytes. It seems that stem cells and proliferating cells in the normal marrow are the source of NS expression detected in normal marrow. NS expreesion in bone marrow of APL patients was significantly higher than normal marrow. In these patients before treatment marrow is replaced by undifferentiated blasts and promyelocytes. We concluded that NS expression in these cells were high. It had been shown that NS down regulation may lead to cell cycle exit. High expression of NS in APL patients can be used in future researches for finding new targeted therapies in this disease. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
1997 ◽  
Vol 89 (10) ◽  
pp. 3596-3606 ◽  
Author(s):  
Troy D. Randall ◽  
Irving L. Weissman

Abstract A significant fraction of hematopoietic stem cells (HSCs) have been shown to be resistant to the effects of cytotoxic agents such as 5-fluorouracil (5-FU), which is thought to eliminate many of the rapidly dividing, more committed progenitors in the bone marrow and to provide a relatively enriched population of the most primitive hematopoietic progenitor cells. Although differences between 5-FU–enriched progenitor populations and those from normal bone marrow have been described, it remained unclear if these differences reflected characteristics of the most primitive stem cells that were revealed by 5-FU, or if there were changes in the stem-cell population itself. Here, we have examined some of the properties of the stem cells in the bone marrow before and after 5-FU treatment and have defined several activation-related changes in the stem-cell population. We found that long-term reconstituting stem cells decrease their expression of the growth factor receptor c-kit by 10-fold and increase their expression of the integrin Mac-1 (CD11b). These changes begin as early as 24 hours after 5-FU treatment and are most pronounced within 2 to 3 days. This activated phenotype of HSCs isolated from 5-FU–treated mice is similar to the phenotype of stem cells found in the fetal liver and to the phenotype of transiently repopulating progenitors in normal bone marrow. We found that cell cycle is induced concomitantly with these physical changes, and within 2 days as many as 29% of the stem-cell population is in the S/G2/M phases of the cell cycle. Furthermore, when examined at a clonal level, we found that 5-FU did not appear to eliminate many of the transient, multipotent progenitors from the bone marrow that were found to be copurified with long-term repopulating, activated stem cells. These results demonstrate the sensitivity of the hematopoietic system to changes in its homeostasis and correlate the expression of several important surface molecules with the activation state of HSCs.


2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Paulina Gil-Kulik ◽  
Arkadiusz Krzyżanowski ◽  
Ewa Dudzińska ◽  
Jolanta Karwat ◽  
Piotr Chomik ◽  
...  

The BIRC5 gene encodes a survivin protein belonging to class III of inhibitors of apoptosis, IAP. This protein serves a dual role. First, it regulates cell death, and second, it is an important regulator of mitosis progression, although its physiological regulatory function has not been fully understood. Many studies have shown and confirmed that survivin is practically absent in mature tissues in nature, while its overexpression has been reported in many cancerous tissues. There is little information about the significance of BIRC5 expression in normal adult human stem cells. This paper presents the study and analysis of survivin expression at the transcription level using qPCR method, in hematopoietic stem cells from peripheral blood mobilized with a granulocyte growth factor, adherent cells derived from the umbilical cord, and normal bone marrow stem cells. The expression of this gene was also examined in the blood of normal healthy individuals. The results of the analysis have shown that the more mature the cells are, the lower the expression of the BIRC5 gene is. The lowest expression has been found in peripheral blood cells, while the highest in normal bone marrow cells. The more the CD34+ and CD105 cells in the tested material are, the higher the BIRC5 expression is. Stem cells from cell culture show higher BIRC5 expression. The study confirms the involvement of BIRC5 from the IAP family in many physiological processes apart from apoptosis inhibition. The possible effect of BIRC5 on cell proliferation; involvement in cell cycle, cell differentiation, survival, and maintenance of stem cells; and the possible effect of IAP on the antineoplastic properties of mesenchymal stem cells have been demonstrated. Our research suggests that BIRC5 may be responsible for the condition of stem cell pluripotency and its high expression may also be responsible for the dedifferentiation of tumor cells.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4368-4368
Author(s):  
Carin L.E. Hazenberg ◽  
Fiona A.J. van den Heuvel ◽  
Ben N.G. Giepmans ◽  
Jan Jacob Schuringa ◽  
Edo Vellenga

Abstract Autologous stem cell transplantation (ASCT) is a frequently applied treatment modality for patients with multiple myeloma (MM) and (relapsing) malignant lymphomas. Normal peripheral blood cell counts are usually observed 1 year post ASCT although the hematopoietic stem cell (HSC) compartment is severely impaired reflected by reduced HSC frequency and quiescence (Haematologica 2013;98:1264). Since HSCs interact intensively with the surrounding microenvironment in the bone marrow and strongly depend on these cells for a proper function, we studied the mesenchymal stem cell (MSC) compartment in patients 1 year post ASCT. We generated a biobank with patient material acquired 1 year after ASCT. Immunohistological studies of bone marrow biopsies post ASCT showed increased expression of CD271 (Nerve Growth Factor Receptor, NGFR) compared to normal bone marrow (NBM, 11.26%±1.2 of bone marrow area versus 1.87%±0.9, p<0.0001) while no difference was observed for the percentage of nestin+ or perivascular CD146+ (Melanoma Cell Adhesion Molecule, MCAM) cells. In addition an increase in CD271+-multilocular adipocytes was noted, reflecting a difference in preferential MSC differentiation. Subsequently MSCs were cultured from the CD34- fraction of the bone marrow mononuclear cells, obtained from post ASCT patients (n=11) and compared to healthy subjects (n=17). MSCs were selected by their plastic-adherency and subsequently replated to generate MSCs. Cultured MSCs from post ASCT and NBM had similar population doubling times (1.92±0.22 and 3.52±1.02 in P4 (passage 4) respectively). In addition no difference in cell surface expression of CD146 and CD271 was demonstrated on MSCs post ASCT as compared to NBM. However, the post ASCT MSCs showed a change in morphology at early passages (P3-4) and premature exhaustion of growth in 45% of the studied patients (n=11) at P5, in contrast to 18% from NBM (n=11). B-galactosidase staining of post ASCT MSCs was increased in P5 and P6 compared to NBM MSCs (20.08%±3.0 vs 9.9%±1.1, p=0.04). To study the functionality of these MSCs, post ASCT MSCs from a low passage (P3 or P4) were used for co-culture experiments with CD34+ cord blood cells in the presence of cytokines SCF, FLT3 and TPO. Co-cultures with MSCs from different post ASCT patients showed a large variation in number of cobblestone-area forming cells (CAFCs, range: 11-163, mean: 81.3±16.0) as well as the size of cobblestone area. This reflects the diversity in HSC support by post ACST MSCs and concurs with the diversity found between patients in the clinical setting. Finally gene profiling performed on cultured post ASCT (n=10) and NBM (n=9) MSCs in early passages (P2 and P3) showed upregulation of proinflammatory genes such as interleukin-6 (IL6) and genes involved in Notch and Transforming Growth Factor-ß (TGF-B) signaling such as Hairy and Enhancer of Split-1 (HES1), and Bone Morphogenetic Protein (BMP)1 and BMP4. These findings were confirmed by quantitative PCR. Foxc1 expression, recently linked to maintenance of hematopoietic stem and progenitor cells, was significantly increased in post ASCT MSCs. Collectively, these data indicate changes in the bone marrow niche, especially in the mesenchymal (CD271+) compartment, inducing premature exhaustion and affecting their supportive role for the HSCs. This damage to the niche may account for the reduced bone marrow reserve observed in patients and generate insight into putative therapeutic targets for improving transplantation strategies. Figure 1a,b,c. Figure 1a,b,c. CD271+ expression is significantly increased in post ASCT bone marrow biopsies (b) compared to normal bone marrow (NBM, a). Quantification of CD271 expression in percentage of total bone marrow area by ImageJ software. * p<0.0001 Figure 2a,b,c,d. Figure 2a,b,c,d. Similar expression of CD146 and CD271 on NBM and post ASCT MSCs. Ns: not significant Premature exhaustion of growth in post ASCT (45%) vs NBM (18%) MSCs before P6 Significant increase in B-galactosidase staining in post ASCT MSCs in P5-P6. * p<0.05 Changed morphology of post ASCT MSCs in vitro, representative example in P4 Disclosures No relevant conflicts of interest to declare.


Blood ◽  
1997 ◽  
Vol 89 (10) ◽  
pp. 3596-3606 ◽  
Author(s):  
Troy D. Randall ◽  
Irving L. Weissman

A significant fraction of hematopoietic stem cells (HSCs) have been shown to be resistant to the effects of cytotoxic agents such as 5-fluorouracil (5-FU), which is thought to eliminate many of the rapidly dividing, more committed progenitors in the bone marrow and to provide a relatively enriched population of the most primitive hematopoietic progenitor cells. Although differences between 5-FU–enriched progenitor populations and those from normal bone marrow have been described, it remained unclear if these differences reflected characteristics of the most primitive stem cells that were revealed by 5-FU, or if there were changes in the stem-cell population itself. Here, we have examined some of the properties of the stem cells in the bone marrow before and after 5-FU treatment and have defined several activation-related changes in the stem-cell population. We found that long-term reconstituting stem cells decrease their expression of the growth factor receptor c-kit by 10-fold and increase their expression of the integrin Mac-1 (CD11b). These changes begin as early as 24 hours after 5-FU treatment and are most pronounced within 2 to 3 days. This activated phenotype of HSCs isolated from 5-FU–treated mice is similar to the phenotype of stem cells found in the fetal liver and to the phenotype of transiently repopulating progenitors in normal bone marrow. We found that cell cycle is induced concomitantly with these physical changes, and within 2 days as many as 29% of the stem-cell population is in the S/G2/M phases of the cell cycle. Furthermore, when examined at a clonal level, we found that 5-FU did not appear to eliminate many of the transient, multipotent progenitors from the bone marrow that were found to be copurified with long-term repopulating, activated stem cells. These results demonstrate the sensitivity of the hematopoietic system to changes in its homeostasis and correlate the expression of several important surface molecules with the activation state of HSCs.


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