Prognostic significance of leukopenia at the time of diagnosis in acute myeloid leukemia (AML)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7070-7070
Author(s):  
M. L. Arellano ◽  
E. Winton ◽  
L. Pan ◽  
L. Souza ◽  
S. Sunay ◽  
...  
Keyword(s):  
Cell Surface ◽  
Adhesion Molecules ◽  
De Novo ◽  
Risk Group ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Surface Adhesion

7070 Background: In contrast to the poor prognosis associated with hyperleukocytosis, the prognostic significance of leukopenia at the time of diagnosis of AML is unknown. Methods: Single institution retrospective analysis of 225 consecutive, newly diagnosed AML patients (pts), homogeneously treated between July 1996 and February 2005; and divided into 2 groups based on presenting WBC: < 2,000/uL (30) and > 2,000/uL (195). Simultaneously obtained peripheral blood and marrow blasts were analyzed for cell surface expression of CD34, cKit, CXCR4, PCAM, VLA-2, VLA-3, VLA-4, VLA-5, and FLT3 using flow cytometry. Results: Patients’ characteristics (gender, secondary vs. de novo, and cytogenetic [CTG] risk) were comparable between the 2 groups. Leukopenic AML pts were older (median 56 vs. 53 years, p = 0.02), and had lower induction complete remission [CR] rates: 63% vs. 81% (p = 0.03) by univariate analysis. Induction mortality was 0% for leukopenic and 5% for non-leukopenic pts. In primary refractory pts, median survival was longer for leukopenic (11) vs. non-leukopenic (34) pts: 137 vs. 81 d (p = 0.026). Median follow-up was 22 mos. Event-free (EFS), disease-free (DFS), and overall survivals (OS) were lower in the leukopenic group: 12 vs. 14; 14 vs. 17; and 17 vs. 19 mos, respectively; but did not reach statistical significance. By multivariate analysis, age (p < 0.0001) and CTG risk group (p < 0.0001) were independent predictors of OS, while CTG risk group predicted RFS (p < 0.0001). The level of expression of cell surface adhesion molecules on blood and marrow blasts was comparable for the 2 groups. Conclusions: AML pts presenting with leukopenia have comparable outcomes to those presenting with normal or high WBC despite a lower likelihood of achieving remission. Leukopenic AML did not have over-expression of cell surface adhesion molecules. No significant financial relationships to disclose.

Cytokine-induced cell surface expression of adhesion molecules in vascular endothelial cellsIn vitro

2001 ◽  
Vol 21 (1) ◽  
pp. 68-71 ◽  
Author(s):  
Chen Honghui ◽  
Liu Changqin ◽  
Sun Shenggang ◽  
Mei Yuanwu ◽  
Tong E’tang
Keyword(s):  
Cell Surface ◽  
Adhesion Molecules ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Vascular Endothelial

scholarly journals HLA-E⁎01:03 Allele in Lung Transplant Recipients Correlates with Higher Chronic Lung Allograft Dysfunction Occurrence

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Julie Di Cristofaro ◽  
Mathieu Pelardy ◽  
Anderson Loundou ◽  
Agnès Basire ◽  
Carine Gomez ◽  
...  
Keyword(s):  
Overall Survival ◽  
Retrospective Study ◽  
Viral Infections ◽  
De Novo ◽  
Therapeutic Option ◽  
Univariate Analysis ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Hematopoietic Stem ◽  
The Impact

Lung transplantation (LTx) is a valid therapeutic option for selected patients with end-stage lung disease. HLA-E seems to play a major role in the immune response to different viral infections and to affect transplantation outcome, in Hematopoietic Stem Cell Transplantation, for example. Two nonsynonymous alleles, HLA-E⁎01:01 and HLA-E⁎01:03, have functional differences, involving relative peptide affinity, cell surface expression, and potential lytic activity of NK cells. The aim of this retrospective study was to determine the impact of these two alleles for LTx recipients on anti-HLA alloimmunization risk, overall survival, and chronic rejection (CLAD). HLA-E was genotyped in 119 recipients who underwent LTx from 1998 to 2010 in a single transplantation center. In univariate analysis, both HLA-E homozygous states were associated with impaired overall survival compared to heterozygous HLA-E alleles (p=0.01). In multivariate analysis, HLA-E⁎01:03 allele showed increased CLAD occurrence when compared to homozygous HLA-E⁎01:01 status (HR: 3.563 (CI 95%, 1.016–12),p=0.047). HLA-E allele did not affect pathogen infection or the production ofde novoDSA. This retrospective study shows an uninvestigated, deleterious association of HLA-E alleles with LTx and requires verification using a larger cohort.

A Cell-Based Adhesion Molecule Bioassay Detects Unexpected Properties of Plasma From Patients with Sickle Cell Disease with Documented Pulmonary Hypertension

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2120-2120
Author(s):  
Antje Ask ◽  
Laurel G. Mendelsohn ◽  
Shoaib Alam ◽  
Alem Mehari ◽  
Caterina Minniti ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Cell Adhesion ◽  
Cell Surface ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Heart Catheterization ◽  
Soluble Adhesion Molecules

Abstract Abstract 2120 Pulmonary hypertension (PH) is a common complication in adults with sickle cell disease (SCD) associated with early mortality. Several mechanistic pathways appear to be involved in PH in SCD, one of them being activation of pulmonary endothelium and increased adherence of circulation blood cells. In the past, levels of soluble adhesion molecules in the plasma of patients with SCD have been found to correlate with severity of pulmonary hypertension and risk of mortality. We investigated the association between endothelial-cell based adhesion molecules and markers of PH. We developed a new cell-based ELISA assay and evaluated the induction of cell surface expression of adhesion molecules on cultured microvascular endothelium cells by plasma from subjects with SCD who had undergone right heart catheterization. We found no difference in baseline Intercellular Cell Adhesion Molecule-1 (ICAM-1), Vascular Cell Adhesion Molecule-1 (VCAM-1) and P-selectin induction by SCD plasma compared to healthy controls. Surprisingly, we found an inverse relationship of cell surface VCAM-1 induction with diagnosis and severity of PH, as indicated by mean pulmonary artery pressure (mPAP) on right heart catheterization. Patients who fell into the upper quartile of VCAM-1 induction had mPAP of 27.6 ± 3.2 mmHg, compared to the middle two quartiles 32 ± 2.3 mmHg, and lower quartile 38.2 ± 4.0 mmHg, (p=0.034). The prevalence of abnormally high pulmonary vascular resistance (>2 standard deviations above the mean) in the high, medium or low VCAM-1 induction groups was 20%, 35% and 80%, respectively (p=0.0066). We also found statistically significant correlations of cell surface VCAM-1 to cardiac output, transpulmonary gradient, pulse pressure, Doppler echocardiography tricuspid regurgitation velocity (TRV) and a marker of systemic iron overload, serum ferritin. Induced cell surface VCAM-1 expression did not correlate significantly in the same subjects with the plasma level of soluble VCAM-1, a previously documented marker associated with high TRV. We found very similar patterns of induction of cell surface expression of P-selectin. These results indicate that the ability of plasma to induce cell surface expression of cell adhesion molecules is a new marker predictive of the diagnosis of catheterization-proven PH in SCD, but it is independent of the levels of the soluble ectodomains of these cell adhesion molecules. These results are consistent with recent publications in the cell adhesion molecule field indicating that independent inflammation-mediated mechanisms regulate adhesion molecule expression and its ectodomain shedding via sheddases. Our findings lead us to speculate that increased sheddase activity may contribute to the high levels of soluble adhesion molecules found in PH, simultaneously reducing the level of cell surface adhesion molecules. Future studies of sheddase activity in SCD PH would help to elucidate this interesting observation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Phosphorylation and internalization of gp130 occur after IL-6 activation of Jak2 kinase in hepatocytes.

1994 ◽  
Vol 5 (7) ◽  
pp. 819-828 ◽  
Author(s):  
Y Wang ◽  
G M Fuller
Keyword(s):  
Protein Synthesis ◽  
Cell Surface ◽  
De Novo ◽  
Cell Types ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Protein Synthesis Inhibitors ◽  
Different Cell Types ◽  
Kinetics Of

Recent evidence has shown that members of the Jak kinase family are activated after IL-6 binds to its receptor complex, leading to a tyrosine phosphorylation of gp130, the IL-6 signal-transducing subunit. The different members of the IL-6 cytokine subfamily induce distinct patterns of Jak-Tyk phosphorylation in different cell types. Using monospecific antibodies to gp130, Jak2 kinase, and phosphotyrosine, we investigated the kinetics of IL-6 stimulation of members of this pathway in primary hepatocytes. Our findings show that Jak 2 is maximally activated within 2 min of exposure to IL-6, followed by gp130 phosphorylation that reaches its peak in another 2 min then declines to basal level by 60 min. In vitro phosphorylation experiments show that activated Jak 2 is able to phosphorylate both native gp130 and a fusion peptide containing its cytoplasmic domain, demonstrating gp130 is a direct substrate of Jak 2 kinase. Experiments designed to explore the cell surface expression of gp130 show that > or = 2 h are required to get a second round of phosphorylation after the addition of more cytokines. This finding suggests that activated gp130 is internalized from the cell surface after IL-6 stimulation. Additional experiments using protein synthesis inhibitors reveal that new protein synthesis is required to get a second cycle of gp130 phosphorylation indicating gp130 must be synthesized de novo and inserted into the membrane. These findings provide strong evidence that down regulation of the IL-6 signal in hepatocytes involves the internalization and cytosol degradation of gp130.

Apical membrane and intracellular distribution of endogenous alpha 2A-adrenergic receptors in MDCK cells

1994 ◽  
Vol 267 (3) ◽  
pp. F347-F353 ◽  
Author(s):  
M. D. Okusa ◽  
K. R. Lynch ◽  
D. L. Rosin ◽  
L. Huang ◽  
Y. Y. Wei
Keyword(s):  
Cell Surface ◽  
De Novo ◽  
Mdck Cells ◽  
Specific Binding ◽  
Surface Expression ◽  
Surface Proteins ◽  
Cell Surface Expression ◽  
Surface Binding ◽  
Binding Studies ◽  
Apical Domain

The purpose of the current studies was to characterize the endogenous alpha 2-adrenergic receptor (AR) subtypes present in Madin-Darby canine kidney (MDCK) cells and to determine their level of expression and pattern of distribution. By saturation binding analysis with [3H]MK-912, MDCK cells expressed high levels of alpha 2-ARs with a maximum receptor density (Bmax) of 798 +/- 55 fmol/mg protein and an equilibrium dissociation constant (Kd) of 0.98 +/- 0.32 nM. Competitive binding studies using prazosin, oxymetazoline, phentolamine, and epinephrine to displace [3H]MK-912 demonstrated inhibition constant (Ki) values of 1,270 +/- 250, 5.0 +/- 0.4, 5.5 +/- 0.3, and 392 +/- 150 nM (n = 3), respectively. In Northern blot analysis we found that MDCK cells expressed transcripts encoding alpha 2A-AR and not alpha 2B-AR or alpha 2C-AR. Surface binding experiments suggested that approximately 60% of alpha 2A-ARs are distributed at the cell surface domain. Specific binding of [3H]MK-912 to soluble apical and basolateral surface proteins isolated by surface biotinylation indicated the expression of surface alpha 2A-ARs was limited to the apical domain of MDCK cells. No alpha 2A-ARs were detected on the basolateral surface. We conclude that endogenous alpha 2A-ARs are targeted to the apical domain of MDCK cells and that the intracellular compartment may contain ARs as a reservoir for de novo cell surface expression or, alternatively, may represent internalized receptors.

Clinical relevance of CD44 cell-surface expression and N-myc gene amplification in a multicentric analysis of 121 pediatric neuroblastomas.

1996 ◽  
Vol 14 (1) ◽  
pp. 25-34 ◽  
Author(s):  
V Combaret ◽  
N Gross ◽  
C Lasset ◽  
D Frappaz ◽  
G Peruisseau ◽  
...  
Keyword(s):  
Cell Surface ◽  
Univariate Analysis ◽  
Surface Expression ◽  
Tumor Stage ◽  
Surface Glycoprotein ◽  
Cell Surface Expression ◽  
Cell Surface Glycoprotein ◽  
Cd44 Expression ◽  
Tumor Stages ◽  
Initial Staging

PURPOSE In contrast to other human tumors, a repression of the cell-surface glycoprotein CD44 on neuroblastoma is a marker of aggressiveness that usually correlates to N-myc amplification. We thus compared the prognostic value of both markers in the initial staging of 121 children treated for neuroblastoma in collaborative institutions. METHODS Frozen samples were analyzed by a rapid and well-standardized technique of immunostaining with monoclonal antibodies (MoAbs) against epitopes in the CD44 constant region. RESULTS In this retrospective series, CD44 was expressed on 102 specimens and strongly correlated with favorable tumor stages and histology, younger age, and normal N-myc copy numbers. In univariate analysis, CD44 expression and normal N-myc were the most powerful markers of favorable clinical outcome (P < 10(-6) and chi 2 = 65.40 and P < 10(-6) and chi 2 = 42.56, respectively), but analysis of CD44 affords significant prognostic discrimination in subgroups of patients with or without N-myc-amplified tumors. In the subgroup of stage IV neuroblastomas, CD44 was the only significant prognostic marker (P < .02, chi 2 = 5.76), whereas N-myc status was not discriminant. In multivariate analysis of five factors, ie, N-myc amplification, CD44 expression, age, tumor stage, and histology, the only independent prognostic factors of event-free survival were CD44 expression and tumor stage. CONCLUSION The analysis of CD44 cell-surface expression must be recommended as an additional biologic marker in the initial staging of the disease.

scholarly journals Human cytomegalovirus suppresses Fas expression and function

2014 ◽  
Vol 95 (4) ◽  
pp. 933-939 ◽  
Author(s):  
Sepehr Seirafian ◽  
Virginie Prod’homme ◽  
Daniel Sugrue ◽  
James Davies ◽  
Ceri Fielding ◽  
...  
Keyword(s):  
Cell Surface ◽  
Human Cytomegalovirus ◽  
De Novo ◽  
Late Phase ◽  
Surface Expression ◽  
Productive Infection ◽  
Cell Surface Expression ◽  
Trail Receptor ◽  
Infected Cells ◽  
High Level

Human cytomegalovirus (HCMV) is known to evade extrinsic pro-apoptotic pathways not only by downregulating cell surface expression of the death receptors TNFR1, TRAIL receptor 1 (TNFRSF10A) and TRAIL receptor 2 (TNFRSF10B), but also by impeding downstream signalling events. Fas (CD95/APO-1/TNFRSF6) also plays a prominent role in apoptotic clearance of virus-infected cells, so its fate in HCMV-infected cells needs to be addressed. Here, we show that cell surface expression of Fas was suppressed in HCMV-infected fibroblasts from 24 h onwards through the late phase of productive infection, and was dependent on de novo virus-encoded gene expression but not virus DNA replication. Significant levels of the fully glycosylated (endoglycosidase-H-resistant) Fas were retained within HCMV-infected cells throughout the infection within intracellular membranous structures. HCMV infection provided cells with a high level of protection against Fas-mediated apoptosis. Downregulation of Fas was observed with HCMV strains AD169, FIX, Merlin and TB40.

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