scholarly journals Identification of Adrenomedullin-Induced S-Nitrosylated Proteins in JEG-3 Placental Cells

2021 ◽  
Author(s):  
Yingting Li ◽  
Liuying Zhong ◽  
Cheuk-Lun Lee ◽  
Philip C.N. Chiu ◽  
Min Chen
Keyword(s):  
Cell Surface ◽  
Cell Invasion ◽  
Surface Expression ◽  
Translation Initiation Factor ◽  
Cell Surface Receptor ◽  
Initiation Factor ◽  
Trophoblast Invasion ◽  
Spectrometric Analysis ◽  
Nitric Oxide Signaling ◽  
Placental Cells

AbstractExtravillous cytotrophoblast (EVCT) is responsible for trophoblast invasion, which is important during placentation. Dysregulation of the process leads to pregnancy complications. S-nitrosylation of proteins is associated with cell invasion in many cell types. Adrenomedullin (ADM), a polypeptide expressed abundantly in the first-trimester placentas, induces EVCT invasion by upregulation of protein S-nitrosylation. This study aimed to identify the S-nitrosylated proteins induced by ADM in the JEG-3 placental cells. By using affinity chromatography followed by mass spectrometric analysis, tubulin, enolase, eukaryotic translation initiation factor 4A1, actin, annexin II (ANX II), and glyceraldehyde 3-phosphate dehydrogenaseprotein-1 were found to be S-nitrosylated by ADM. In vitro treatment with ADM or S-Nitrosoglutathione (GSNO) significantly increased the ANX II surface expression, but not its total expression in the JEG-3 cells. Translocation of ANX II to cell surface has been reported to act as a cell surface receptor to plasmin, plasminogen, and tissue plasminogen activator (tPA), thereby stimulating cell invasion and migration. However, in this study, ADM-induced surface expression of ANX II in the JEG-3 cells was not associated with changes in the secretory and membrane-bound tPA activities. Future studies are required to understand the roles of surface expression of S-nitrosylated ANX II on trophoblast functions. To conclude, this study provided evidences that ADM regulated the nitric oxide signaling pathway and modulated trophoblast invasion.

scholarly journals Dectin-1-Mediated Production of Pro-Inflammatory Cytokines Induced by Yeast β-Glucans in Bovine Monocytes

2021 ◽  
Vol 12 ◽  
Author(s):  
Ana R. V. Pedro ◽  
Tânia Lima ◽  
Ricardo Fróis-Martins ◽  
Bárbara Leal ◽  
Isabel C. Ramos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Surface ◽  
Inflammatory Cytokines ◽  
Surface Expression ◽  
Cell Surface Receptor ◽  
Dependent Manner ◽  
Feed Supplements ◽  
Surface Receptor ◽  
Dose Dependent ◽  
Pro Inflammatory Cytokines

Yeast-derived products containing β-glucans have long been used as feed supplements in domesticated animals in an attempt to increase immunity. β-glucans are mainly recognized by the cell surface receptor CLEC7A, also designated Dectin-1. Although the immune mechanisms elicited through Dectin-1 activation have been studied in detail in mice and humans, they are poorly understood in other species. Here, we evaluated the response of bovine monocytes to soluble and particulate purified β-glucans, and also to Zymosan. Our results show that particulate, but not soluble β-glucans, can upregulate the surface expression of costimulatory molecules CD80 and CD86 on bovine monocytes. In addition, stimulated cells increased production of IL-8 and of TNF, IL1B, and IL6 mRNA expression, in a dose-dependent manner, which correlated positively with CLEC7A gene expression. Production of IL-8 and TNF expression decreased significantly after CLEC7A knockdown using two different pairs of siRNAs. Overall, we demonstrated here that bovine monocytes respond to particulate β-glucans, through Dectin-1, by increasing the expression of pro-inflammatory cytokines. Our data support further studies in cattle on the induction of trained immunity using dietary β-glucans.

Effect of aging on CD11b and CD69 surface expression by vesicular insertion in human polymorphonuclear leucocytes

1999 ◽  
Vol 97 (3) ◽  
pp. 323-329 ◽  
Author(s):  
J. M. NOBLE ◽  
G. A. FORD ◽  
T. H. THOMAS
Keyword(s):  
Plasma Membrane ◽  
Cell Surface ◽  
Surface Expression ◽  
Cell Surface Receptor ◽  
Cell Surface Expression ◽  
Elderly Subjects ◽  
Polymorphonuclear Leucocytes ◽  
Cd11b Expression ◽  
Cd69 Expression ◽  
Vesicle Exocytosis

The exocytosis of intracellular vesicles is an important function of the plasma membrane, which is responsible for hormone secretion, cell surface expression of antigens, ion transporters and receptors, and intracellular and intercellular signalling. Human aging is associated with many physiological and cellular changes, many of which are due to alterations in plasma membrane functioning. Alterations in vesicle externalization with age could account for many of these changes. We investigated whether alterations in vesicle exocytosis occur with increasing age by flow-cytometric determination of CD11b and CD69 expression on the surface of human polymorphonuclear leucocytes (PMN) stimulated with phorbol myristate acetate (PMA), a tumour promoter which binds to and activates protein kinase C (PKC) directly, or with formyl-Met-Leu-Phe (fMLP), which activates PKC indirectly via interactions with a cell surface receptor and G-protein, and subsequent inositol phosphate hydrolysis. Following stimulation with PMA, a decrease in the proportion of PMN expressing CD69 at high levels was observed in elderly compared with young subjects (young, 55.3%; elderly, 43.9%; P = 0.01). No aging-related differences in the proportion of PMN expressing CD11b (young, 73.7%; elderly, 68.4%; P = 0.15), or in the number of molecules of CD69 or CD11b expressed per cell, were observed. Stimulation with fMLP or low PMA concentrations resulted in full CD11b expression but minimal CD69 expression in both young and elderly subjects. Cells which expressed CD69 had no CD11b expression, while those cells expressing CD11b had minimal CD69 expression. Thus the PMA-induced expression of CD11b and CD69 in human PMN represents two separate processes, only one of which is affected in aging. CD11b expression appears to require a lesser degree of PKC stimulation compared with that required for CD69 expression. The age-associated reduction in PMA-stimulated CD69 expression may occur either at or distal to PKC activation. Such a decrease may contribute to the age-associated impairments in PMN function that contribute, in turn, to immunosenescence.

scholarly journals The PAR2 signal peptide prevents premature receptor cleavage and activation

2019 ◽  
Author(s):  
Belinda Liu ◽  
Grace Lee ◽  
Jiejun Wu ◽  
Janise Deming ◽  
Chester Kuei ◽  
...  
Keyword(s):  
Cell Surface ◽  
Signal Peptide ◽  
Synthetic Peptide ◽  
Surface Expression ◽  
Receptor Expression ◽  
Cell Surface Receptor ◽  
Cell Surface Expression ◽  
Peptide Ligand ◽  
Protease Activated Receptors ◽  
N Terminus

AbstractUnlike closely related GPCRs, protease-activated receptors (PAR1, PAR2, PAR3, and PAR4) have a predicted signal peptide at their N-terminus, which is encoded by a separate exon, suggesting that the signal peptides of PARs may serve an important and unique function, specific for PARs. In this report, we show that the PAR2 signal peptide, when fused to the N-terminus of IgG-Fc, effectively induced IgG-Fc secretion into culture medium, thus behaving like a classical signal peptide. The presence of PAR2 signal peptide has a strong effect on PAR2 cell surface expression, as deletion of the signal peptide (PAR2ΔSP) led to dramatic reduction of the cell surface expression and decreased responses to trypsin or the synthetic peptide ligand (SLIGKV). However, further deletion of the tethered ligand region (SLIGKV) at the N-terminus rescued the cell surface receptor expression and the response to the synthetic peptide ligand, suggesting that the signal peptide of PAR2 may be involved in preventing PAR2 from intracellular protease activation before reaching the cell surface. Supporting this hypothesis, an Arg36Ala mutation on PAR2ΔSP, which disabled the trypsin activation site, increased the receptor cell surface expression and the response to ligand stimulation. Similar effects were observed when PAR2ΔSP expressing cells were treated with protease inhibitors. Our findings indicated that these is a role of the PAR2 signal peptide in preventing the premature activation of PAR2 from intracellular protease cleavage before reaching the cells surface. The same mechanism may also apply to PAR1, PAR3, and PAR4.

scholarly journals Proteomic Analysis of Rickettsia parkeri Strain Portsmouth

2009 ◽  
Vol 77 (12) ◽  
pp. 5262-5271 ◽  
Author(s):  
Walairat Pornwiroon ◽  
Apichai Bourchookarn ◽  
Christopher D. Paddock ◽  
Kevin R. Macaluso
Keyword(s):  
Cell Surface ◽  
Vaccine Development ◽  
Spotted Fever ◽  
The United States ◽  
Trna Synthetase ◽  
Surface Proteins ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Two Dimensional ◽  
Rickettsia Parkeri

ABSTRACT Rickettsia parkeri, a recently recognized pathogen of human, is one of several Rickettsia spp. in the United States that causes a spotted fever rickettsiosis. To gain insights into its biology and pathogenesis, we applied the proteomics approach to establish a two-dimensional gel proteome reference map and combined this technique with cell surface biotinylation to identify surface-exposed proteins of a low-passage isolate of R. parkeri obtained from a patient. We identified 91 proteins by matrix-assisted laser desorption ionization-tandem time of flight mass spectrometry. Of these, 28 were characterized as surface proteins, including virulence-related proteins (e.g., outer membrane protein A [OmpA], OmpB, β-peptide, and RickA). Two-dimensional immunoblotting with serum from the R. parkeri-infected index patient was utilized to identify the immunoreactive proteins as potential targets for diagnosis and vaccine development. In addition to the known rickettsial antigens, OmpA and OmpB, we identified translation initiation factor 2, cell division protein FtsZ, and cysteinyl-tRNA synthetase as immunoreactive proteins. The proteome map with corresponding cell surface protein analysis and antigen detection will facilitate a better understanding of the mechanisms of rickettsial pathogenesis.

scholarly journals Role of Asparagine-Linked Glycosylation in Cell Surface Expression and Function of the Human Adrenocorticotropin Receptor (Melanocortin 2 Receptor) in 293/FRT Cells

Endocrinology ◽  
2010 ◽  
Vol 151 (2) ◽  
pp. 660-670 ◽  
Author(s):  
Simon Roy ◽  
Benoît Perron ◽  
Nicole Gallo-Payet
Keyword(s):  
Cell Surface ◽  
Fold Increase ◽  
Surface Expression ◽  
Site Directed Mutagenesis ◽  
Cell Surface Receptor ◽  
Cell Surface Expression ◽  
Camp Production ◽  
Glycosylation Sites ◽  
Surface Receptor

Asparagine-linked glycosylation (N-glycosylation) of G protein-coupled receptors may be necessary for functions ranging from agonist binding, folding, maturation, stability, and internalization. Human melanocortin 2 receptor (MC2R) possesses putative N-glycosylation sites in its N-terminal extracellular domain; however, to date, the role of MC2R N-glycosylation has yet to be investigated. The objective of the present study is to examine whether N-glycosylation is essential or not for cell surface expression and cAMP production in native and MC2R accessory protein (MRAPα, -β, or -dCT)-expressing cells using 293/FRT transfected with Myc-MC2R. Western blot analyses performed with or without endoglycosidase H, peptide:N-glycosidase F or tunicamycin treatments and site-directed mutagenesis revealed that MC2R was glycosylated in the N-terminal domain at its two putative N-glycosylation sites (Asn12-Asn13-Thr14 and Asn17-Asn18-Ser19). In the absence of human MRAP coexpression, N-glycosylation of at least one of the two sites was necessary for MC2R cell surface expression. However, when MRAP was present, cell surface expression of MC2R mutants was either rescued entirely with the N17-18Q (QQNN) and N12-13Q (NNQQ) mutants or partially with the unglycosylated N12-13, 17-18Q (QQQQ) mutant. Functional and expression analyses revealed a discrepancy between wild-type (WT) and QQQQ cell surface receptor levels and maximal cAMP production with a 4-fold increase in EC50 values. Taken together, these results indicate that the absence of MC2R N-glycosylation abrogates to a large extent MC2R cell surface expression in the absence of MRAPs, whereas when MC2R is N-glycosylated, it can be expressed at the plasma membrane without MRAP assistance.

scholarly journals Adenovirus RIDαβ Complex Inhibits Lipopolysaccharide Signaling without Altering TLR4 Cell Surface Expression

2006 ◽  
Vol 80 (13) ◽  
pp. 6378-6386 ◽  
Author(s):  
Fernando Delgado-Lopez ◽  
Marshall S. Horwitz
Keyword(s):  
Signal Transduction ◽  
Cell Surface ◽  
Signaling Pathways ◽  
Interleukin 1 ◽  
Mechanistic Explanation ◽  
Surface Expression ◽  
Receptor Internalization ◽  
Cell Surface Receptor ◽  
Cell Surface Expression ◽  
Down Regulation

ABSTRACT The transmembrane heterotrimer complex 10.4K/14.5K, also known as RID (for “receptor internalization and degradation”), is encoded by the adenovirus E3 region, and it down-regulates the cell surface expression of several unrelated receptors. We recently showed that RID expression correlates with down-regulation of the cell surface expression of the tumor necrosis factor (TNF) receptor 1 in several human cells. This observation provided the first mechanistic explanation for the inhibition of TNF alpha-induced chemokines by RID. Here we analyze the immunoregulatory activities of RID on lipopolysaccharide (LPS) and interleukin-1 beta (IL-1β)-mediated responses. Although both signaling pathways are strongly inhibited by RID, the chemokines up-regulated by IL-1β stimulation are only marginally inhibited. In addition, RID inhibits signaling induced by LPS without affecting the expression of the LPS receptor Toll-like receptor 4, demonstrating that RID need not target degradation of the receptor to alter signal transduction. Taken together, our data demonstrate the inhibitory effect of RID on two additional cell surface receptor-mediated signaling pathways involved in inflammatory processes. The data suggest that RID has intracellular targets that impair signal transduction and chemokine expression without evidence of receptor down-regulation.

scholarly journals Eimeria tenella Translation Initiation Factor eIF-5A That Interacts With Calcium-Dependent Protein Kinase 4 Is Involved in Host Cell Invasion

2021 ◽  
Vol 10 ◽  
Author(s):  
Shanshan Liang ◽  
Hui Dong ◽  
Shunhai Zhu ◽  
Qiping Zhao ◽  
Bing Huang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Translation Initiation ◽  
Cell Invasion ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Host Cell Invasion ◽  
Dependent Protein Kinase ◽  
Calcium Dependent ◽  
Dependent Protein ◽  
Calcium Dependent Protein Kinase

Eimeria tenella is an apicomplexan, parasitic protozoan known to infect poultry worldwide. An important calcium-dependent protein kinase (CDPK) has been identified in plants, green algae, ciliates and apicomplexan, such as E. tenella. CDPKs are effector molecules involved in calcium signaling pathways, which control important physiological processes such as gliding motility, reproduction, and host cell invasion. Given that CDPKs are not found in the host, studying the functions of CDPKs in E. tenella may serve as a basis for developing new therapeutic drugs and vaccines. To assess the function of CDPK4 in E. tenella (EtCDPK4), a putative interactor, translation initiation factor eIF-5A (EteIF-5A), was screened by both co-immunoprecipitation (co-IP) and His pull-down assays followed by mass spectrometry. The interaction between EteIF-5A and EtCDPK4 was determined by bimolecular fluorescence complementation (BiFC), GST pull-down, and co-IP. The molecular characteristics of EteIF-5A were then analyzed. Quantitative real-time polymerase chain reaction and western blotting were used to determine the transcription and protein levels of EteIF-5A in the different developmental stages of E. tenella. The results showed that the transcription level of EteIF-5A mRNA was highest in second-generation merozoites, and the protein expression level was highest in unsporulated oocysts. Indirect immunofluorescence showed that the EteIF-5A protein was found throughout the cytoplasm of sporozoites, but not in the refractile body. As the invasion of DF-1 cells progressed, EteIF-5A fluorescence intensity increased in trophozoites, decreased in immature schizonts, and increased in mature schizonts. The secretion assay results, analyzed by western blotting, indicated that EteIF-5A was a secreted protein but not from micronemes. The results of invasion inhibition assays showed that rabbit anti-rEteIF-5A polyclonal antibodies effectively inhibited cell invasion by sporozoites, with an inhibition rate of 48%.

Biochemical characterization of PRV-1, a novel hematopoietic cell surface receptor, which is overexpressed in polycythemia rubra vera

Blood ◽  
2002 ◽  
Vol 100 (7) ◽  
pp. 2441-2448 ◽  
Author(s):  
Steffen Klippel ◽  
Elisabeth Strunck ◽  
Christian E. Busse ◽  
Dirk Behringer ◽  
Heike L. Pahl
Keyword(s):  
Cell Surface ◽  
Polycythemia Vera ◽  
Biochemical Characterization ◽  
Mrna Level ◽  
Alternative Polyadenylation ◽  
Surface Expression ◽  
Cell Surface Receptor ◽  
Rich Domain ◽  
Significant Difference ◽  
Polycythemia Rubra Vera

The cDNA for polycythemia rubra vera 1 (PRV-1), a novel hematopoietic receptor, was recently cloned by virtue of its overexpression in patients with polycythemia vera. PRV-1 is a member of the uPAR/CD59/Ly6 family of cell surface receptors, which share a common cysteine-rich domain and are tethered to the cell surface via a glycosylphosphatidylinositol (GPI) link. We have determined the intron-exon structure of the PRV1gene and show that the locus is structurally intact in patients with polycythemia vera. Thus, PRV-1 overexpression in these patients is not due to rearrangement or structural alteration of the gene. Northern blot analysis detects multiple PRV-1 transcripts. Here we show that these transcripts arise from alternative polyadenylation and encode the same protein. Biochemical analysis reveals that PRV-1 isN-glycosylated and embedded in the cell membrane by a lipid anchor, like other members of this family. Moreover, PRV-1 is shed from the cell surface because soluble protein can be detected in cell supernatants. Fluorescence-activated cell sorting analysis of stably transfected cells revealed that PRV-1 is recognized by antibodies directed against the neutrophil antigen NB1/CD177. Flow cytometry of bone marrow and peripheral blood of both healthy donors and patients with polycythemia vera showed that PRV-1 protein is expressed on myeloid cells of the granulocytic lineage. However, unlike the significant difference in PRV-1 expression observed on the mRNA level, the amount of PRV-1 protein on the cell surface is not consistently elevated in patients with polycythemia vera compared with healthy controls. Therefore, quantification of PRV-1 surface expression cannot be used for the diagnosis of polycythemia vera.

scholarly journals Cancer-Associated Mutations Reveal a Novel Role for EpCAM as an Inhibitor of Cathepsin-L and Tumor Cell Invasion

2020 ◽  
Author(s):  
Narendra Sankpal ◽  
Taylor C. Brown ◽  
Timothy P. Fleming ◽  
John M. Herndon ◽  
Anusha A. Amaravati ◽  
...  
Keyword(s):  
Cell Surface ◽  
Tumor Cell ◽  
Cell Invasion ◽  
Cancer Biology ◽  
Human Cancer ◽  
Cathepsin L ◽  
Surface Expression ◽  
Tumor Cell Invasion

Abstract BackgroundEpithelial cell adhesion molecule (EpCAM) is a 40-kD type-I transmembrane protein that is frequently overexpressed in human epithelial cancers. Recent evidence implicates EpCAM in the regulation of oncogenic signaling pathways and epithelial-mesenchymal transition. Of note, multiple proteins with thyroglobulin-type-1 (TY-1) domains are known to inhibit cathepsin-L (CTSL), a cysteine protease that promotes tumor invasion and metastasis.MethodsHuman cancer sequencing studies reveal that somatic EpCAM mutations are present in up to 5.1% of tested tumors form public database search. To determine how EpCAM mutations affect cancer biology we studied C66Y, a damaging TY-1 domain mutation identified in liver cancer, as well as 13 other cancer-associated EpCAM mutations. Using in-vitro and in-vivo models, immunoprecipitations and localizations we demonstrate EpCAM inhibits CTSL activity based mutations and thereby its localization.ResultsWe demonstrate that wild type (WT) EpCAM, but not C66Y EpCAM, inhibits CTSL activity in vitro, and the TY-1 domain of EpCAM is responsible for this inhibition. WT EpCAM, but not C66Y EpCAM, inhibits tumor cell invasion in vitro and lung metastasis in vivo. In an extended panel of human cancer cell lines, EpCAM expression is inversely correlated with CTSL activity. Previous studies have demonstrated that EpCAM germline mutations can prevent EpCAM from being expressed at the cell surface. We demonstrate that C66Y and multiple other EpCAM cancer-associated mutations prevent surface expression of EpCAM. Cancer-associated mutations that prevent EpCAM cell surface expression abrogate the ability of EpCAM to inhibit CTSL activity and tumor cell invasion. ConclusionsThese studies reveal a novel role for EpCAM as a CTSL inhibitor, confirm the functional relevance of multiple cancer-associated EpCAM mutations, and suggest a therapeutic vulnerability in cancers harboring EpCAM mutations.

Expression of 67-Kda Laminin Receptor (67LR) Relates to the Aggressiveness and Poor Prognosis of AML: Modulation of the Expression of GM-CSF Receptor by 67LR.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 926-926
Author(s):  
Koji Ando ◽  
Yasushi Miyazaki ◽  
Daisuke Imanishi ◽  
Masako Iwanaga ◽  
Hideki Tsushima ◽  
...  
Keyword(s):  
Cell Surface ◽  
Poor Prognosis ◽  
Surface Expression ◽  
Laminin Receptor ◽  
Cell Surface Receptor ◽  
High Expression ◽  
Clinical Samples ◽  
Α Subunit ◽  
Gm Csf ◽  
Significant Difference

Abstract Background: The 67-kDa laminin receptor (67LR) is a non-integrin cell surface receptor for laminin, one of the major components of extracellular matrix. Previously (at ASH 2007, PS 2845), we reported that the high expression of 67LR on CD34+AML cells was related with a poor prognosis of AML, and that the forced expression of 67LR resulted in the enhanced proliferation and the resistance against apoptosis of leukemia cells by increasing phosphorylated STAT5. However, there was no information about how the expression of 67LR modulated the signaling of STAT5 pathway. Objective: To elucidate how 67LR enhances the signaling of STAT5 pathway and the role of 67LR in clinical course of AML. Methods: The cDNA or short interfering RNA for LR cloned into various kinds of plasmids was expressed in TF-1 and AML193 leukemia cell lines via stable transfection. As overexpressors of LR, TF-1LR and AML193LR were generated, and as a suppressor of LR, TF-1si. Because it is well known that the signaling of STAT5 pathway was enhancing by GM-CSF signaling, the expression of the GM-CSF receptor α subunit (GM-CSFRα) was analyzed by flowcytometry. To test the interaction between 67LR with V5-tag and GM-CSFRα with Flag-tag protein, we transiently transfected expression plasmids containing cDNA for these protein into human 293T cells. Lysates of these transfected cells were subjected to the immunoprecipitation using anti-V5 or anti-Flag Ab, followed by immunoblotting with HRP conjugated antibodies. From 44 AML patients (M0[2], M1[4], M2[18], M4[11], M5[3], M6[3], MDS/AML[3]), CD34-positive cells were isolated by column method to examine the surface expression of 67LR with flowcytometry. To assess the clinical significance of 67LR expression, 44 pattients with AML were divided into two groups by the surface-expression level of 67LR: 20 cases in the high-expression group (positive in >25% of cells, LR-H) and 24 cases in the low-expression group (LRL). Clinical factors including WBC, LDH, and overall survival were compared between two groups. Results: The surface expression of 67LR was 64% in parental TF-1, 92% in TF-1LR, and 36% in TF-1si, and that was 65% in AML193 and 91% in AML193LR. The surface expression of GM-CSFRα was lower in TF-1si (MFI: 5.1) than its control (MFI:7.3), whereas that was higher in TF-1LR (MFI:19.2) than its control (MFI:7.3). In AML193LR, GM-CSFRα was also higher than the control (MFI:34.7 and 18.9, respectively). These results demonstrated that the modulation of 67LR expression contributed to changes in the level of GM-CSFRα on cell surface. Immunoprecipitation assays indicated that 67LR and GM-CSFRα protein were present in the same protein complex in vivo. In clinical samples, median surface expression of 67LR on CD34 positive AML cells was 17%, and the median intensity of GM-CSFRα was 5.8. We found a significant positive relationship between the surface expression of 67LR and the median intensity of GM-CSFRα on CD34 positive AML cells (chi-square value was 0.04). WBC counts and LDH levels at diagnosis were significantly higher in LR-H group than that in LH-L (p=0.04, p=0.02, respectively). There was a significant difference in survival between LR-L and LR-H groups (median survival 803 and 239 days, respectively, p=0.009). Conclusion: We found the level of 67LR could modulate the expression of GM-CSFRα, thereby it might enhance the phosphorylation of STAT5. Among AML patients, high level of 67LR expression was related to the higher WBC count, elevated LDH and shorter survival. The expression of 67LR and GM-CSFRα in clinical samples also showed significant correlation in amount. These data suggested that the high expression of 67LR resulted in the proliferation of AML cells by increasing the expression of GM-CSFRα. These features could contribute, at least in part, to a poor prognosis of AML.

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