Phenotype Does Not Always Equal Function: HDAC Inhibitors and UM171, but Not SR1, Lead to Rapid Upregulation of CD90 on Non-Engrafting CD34+CD90-Negative Human Cells
Ana Katherine GonçalvesMegan D. HobanJennifer ProctorHillary L. AdamsSharon L. HyzyAnthony E. BoitanoM. Cooke
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CD90
Trichostatin A
Immunophenotyping
Trichostatin A
Histone deacetylase inhibitor
Chromatin immunoprecipitation
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Objective To explore the immunophenotype features of CD34 positive cells in patients with myelodysplastic syndrome(MDS).Methods The immunophenotypes of the CD34 positive cells in bone marrow nuclear cells of 20 patients with MDS were performed with a panel of monoclonal antibodies and four-color flow cytometry by secondary gating strategy.Results With the progression of MDS from RA/RAS,RAEB to RAEBT,the proportion of CD34~+ cells was gradually increased from 7.6%,40.1% to 71.3%(P0.05).Using CD45 vs CD34 gating strategy,the expressions of HLA-DR,CD13,CD33,CD117 on blasts were higher by secondary gating method.However,there were no differences in the expression of above-mentioned antigens on CD34~+ cells in different MDS subtypes(P0.05).Conclusion Secondary gating strategy could accurately reflect the immunophenotype features of blasts in MDS.
Immunophenotyping
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AIM: We studied the expression status and the prognostic significance of progenitor cell markers CD34, CD38, and CD90 in acute myeloid leukemia patients.METHODS: The levels of CD34, CD38, and CD90 on mononuclear cells of bone marrow were determined by flow cytometry from 56 patients, and subjected to statistical analyses for the prognostic correlation.RESULTS: CD34 was highest expressed in undifferentiated leukemia (60% positive cells) and lowest in FAB-type M3 (23% positive cells). CD38 was highly expressed in all FAB types (60-80% positive cells). CD90 was highest expressed in FAB-type M3 (73% positive cells) and lowest in M0 (9% positive cells). No differences in expression were found in different cytogenetic risk groups, in the responder's/non-responder's groups to the therapy, or in different age groups. Cut-off analyses for CD34 and CD90 showed that patients with＞43% CD34(superscript +) cells (P=0.12) and ＜64% CD90(superscript +) cells (P=0.09) had a tendency to a lower probability for relapse-free survival. After 10 months, 45% vs. 80% of patients with＞vs. ＜43% CD34(superscript +) cells were still in remission; 50% of patients with＜64% CD90(superscript +) cells had relapsed after 10 months, whereas all of the patients with＞64% CD90(superscript +) cells were in remission 24 months after first diagnosis.CONCLUSION: Progenitor cell markers like CD34, CD38, and CD90 are variably expressed in all FAB types, cytogenetic risk groups, and on cells from patients who had or had not responded to the therapy. However, amounts of detectable CD34(superscript +) and CD90(superscript +) cells could be predictive for the further course of the disease. This could contribute to differentiate leukemic from non-leukemic cells, to estimate prognosis, and to develop targeted therapies against leukemic antigens.
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Objective:To investigate the influence of histone deacetylase inhibitor(Trichostatin A)to multiplication,invasion, cell cycle of breast cancer MDA-MB-231 cell line.Methods:After 6-48hours treatment with the concentration(100～400nmol/L)of Trichostatin,the growth activity of MDA-MB-231 cell line was detected by MTT.The expression of ERα,MMP-9 mRNA was detected by RT-PCR with different concentration(100～400nmal/L TSA)during 24 hours to MDA-MB-231 cell line.The expression of ERα,MMP-9 protein was examined by immunohistochemistry with different concentration(100～400nmol/L TSA)during 24 hours treatment to MDA-MB-231 cell line.With cell invasion experiment to detect the change of invasive power by using different concentration(100～400nmol/L TSA)during 24 hours to MDA-MB-231 cell line.Results: Trichostatin can inhibit the growth of MDA-MB-231 cell line,which was time and dose dependent.Trichostatin can delay the cell cycle G_2/M stage,stop the cell stage in G_2 stage.Trichostatin can up-regulate the expression of ERαmRNA, down-regulate the expression of MMP-9 mRNA in cells.The invasion experiment indicate that Trichostatin can conspicuous inhibit the invasion of MDA-MB-231 cell line.Conclusions:Trichostatin can inhibit the accrementition,invasion and metastasis of MDA-MB-231 cell line evidently,and one of the mechanism may be the up-regulation of ERαand the down-regulation of MMP-9.
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Bone marrow derived progenitor cells participate in the repair of injured vessels. The lungs of individuals with emphysema have reduced alveolar capillary density and increased endothelial apoptosis. We hypothesized that circulating levels of endothelial and hematopoietic progenitor cells would be reduced in this group of patients.The goal of this study was to measure circulating levels of endothelial progenitor cells (EPCs) and hematopoietic progenitor cells (HPCs) in subjects with COPD and to determine if progenitor levels correlated with disease severity and the presence of emphysema.Peripheral blood mononuclear cells were isolated from 61 patients with COPD and 32 control subjects. Levels of EPCs (CD45(dim) CD34+) and HPCs (CD45(+) CD34(+) VEGF-R2(+)) were quantified using multi-parameter flow cytometry. Progenitor cell function was assessed using cell culture assays. All subjects were evaluated with spirometry and CT scanning.HPC levels were reduced in subjects with COPD compared to controls, whereas circulating EPC levels were similar between the two groups. HPC levels correlated with severity of obstruction and were lowest in subjects with severe emphysema. These associations remained after correction for factors known to affect progenitor cell levels including age, smoking status, the use of statin medications and the presence of coronary artery disease. The ability of mononuclear cells to form endothelial cell colony forming units (EC-CFU) was also reduced in subjects with COPD.HPC levels are reduced in subjects with COPD and correlate with emphysema phenotype and severity of obstruction. Reduction of HPCs may disrupt maintenance of the capillary endothelium, thereby contributing to the pathogenesis of COPD.
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This study was undertaken to determine the effect of short-course high-dose methylprednisolone (HDMP) treatment on peripheral blood (PB) CD34+ progenitor cells during remission induction treatment in 11 children with newly diagnosed acute leukemia (7 with ALL, 4 with AML) whose bone marrow (BM) cells expressed fewer than 5% CD34 at the time of diagnosis. All children who had no infection were given HDMP as a single daily oral dose of 30 mg/kg for the first four days of induction therapy. The number of CD34+ progenitor cells were determined by flow cytometry before and after four days of HDMP treatment. While the number of PB blast cells significantly decreased after only a four-day course of HDMP treatment, the number of PB CD34+ progenitor cells increased in all patients. In addition, after four days of HDMP treatment polymorphonuclear leukocytes (PMN) and mononuclear cells (MNC) increased significantly (p < 0.05). We suggest that the potential beneficial effects of HDMP in the induction treatment of acute leukemia may occur partly by the stimulation of PB CD34+ hematopoietic progenitor cells in a short period of time.
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This study was aimed at exploring the immunophenotypic features of blasts in patients with myelodysplastic syndromes (MDS). Four-color flow cytometry using conventional and secondary gating strategies was used to immunophenotype blasts and the CD34 positive cells in bone marrow nucleated cells of 29 patients with MDS. The results showed: (1) with progression of MDS from RA/RAS, RAEB to RAEB-T, the proportion of CD34(+) cells were gradually increased from 8.0%, 46.4% to 76.8% (P < 0.05); (2) using CD45 vs SSC gating strategy, with the transformation of RA/RAS, RAEB to RAEB-T, the expression of HLA-DR, CD13, CD33, CD117 were also gradually increased (P < 0.05), and the expression of CD15 was gradually decreased (P < 0.05); (3) using CD45 vs CD34 gating strategy, the expression of HLA-DR, CD13, CD33, CD117 on blasts were higher by secondary gating method than those by conventional gating (P < 0.05). However, there were no significant difference (P > 0.05) in the expression of above-mentioned antigens on CD34(+) cells among different MDS subtypes. It is concluded that conventional gating method can reflect MDS progression from RA/RAS, RAEB to RAEB-T, and secondary gating strategy may accurately reflect the biological features of blasts in MDS. Abnormal expression of CD34 is related to the immaturity level and heterogeneity of blast cells, which is beneficial to the diagnosis of clinically suspected MDS incapable of diagnosing with morphology and cytogenetics.
Immunophenotyping
Cytometry
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Trichostatin A
Histone deacetylase inhibitor
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Immunostaining
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Abstract Background: Despite treatment advances, systemic lupus erythematosus (SLE) patients frequently experience disease flares, which can lead to organ damage and premature death. Therefore, assessing disease activity in SLE patients is crucial for adjusting treatment and preventing further organ damage. The aim of this study was to investigate progenitor cells and circulating endothelial cells levels in relation to SLE activity and accumulate organ damage. Methodos: A case-control study was conducted. CD34 + CD45 low/- progenitor cells, CD34 + CD45 low/- CD133 + progenitor, Endothelial Progenitor cells (EPC) and Circulating Endothelial cells (CEC) levels in peripheral blood were assessed by flow cytometry. Results: Thirty-two SLE patients and 28 matched controls were included. SLE patients had lower levels of CD34 + CD45 low/- progenitor cells (p=0.001), CD34 + CD45 low/- CD133 + progenitor cells (p=0.016), EPC (p=0.018) and CEC (p<0.001) compared to controls. In addition, cell subpopulations studied correlate with SLE activity biomarkers. CD34 + CD45 low/- progenitor cells showed a moderate negative correlation with levels of both C3 and C4. We also found significantly higher levels of CD34 + CD45 low/- progenitor cells, CD34 + CD45 low/- CD133 + progenitor cells, EPC and CEC in patients with SLE with SDI scores ≥1 versus those without organ damage (p=0.0073, p=0.018, p=0.018 and p=0.020, respectively). Conclusion: We found that CD34 + CD45 low/- progenitor cells, CD34 + CD45 low/- CD133 + progenitor cells, CPE and CEC were significantly reduced in patients with SLE as well as associated with disease activity and organ damage. Our observations suggest that CD34 + CD45 low/- progenitor cells could serve as a potential biomarker for disease activity and organ damage in SLE patients. It should be confirmed in a prospective study.
Endothelial progenitor cell
Progenitor
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