scholarly journals The role of Src homology region 2 domain-containing phosphatase-1 hypermethylation in the classification of patients with myelodysplastic syndromes and its association with signal transducer and activator of transcription 3 phosphorylation in skm-1 cells

2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199955
Author(s):  
Ying Han ◽  
Jin Zhang ◽  
Yanbin Pang ◽  
Yamei Wang ◽  
Xinying Zhang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Viability ◽  
Myelodysplastic Syndromes ◽  
Bone Marrow Cells ◽  
Prognostic Indicator ◽  
Suppressor Gene ◽  
Signal Transducer ◽  
Homology Region ◽  
Stat3 Phosphorylation ◽  
Src Homology

Introduction Myelodysplastic syndromes (MDS) are a group of heterogeneous bone marrow clonal diseases characterized by the abnormal differentiation and development of bone marrow cells. Src homology region 2 domain-containing phosphatase (SHP)-1 is an important tumor suppressor gene that regulates the signal transducer and activator of transcription (STAT) pathway. Methods Survival analysis was performed to evaluate the function of decitabine (5-Aza) in treating MDS patients with and without SHP-1 methylation. The effects of 5-Aza treatment on SHP-1 expression and methylation and STAT3 phosphorylation were investigated in MDS cells by methylation-specific PCR, reverse transcription PCR, and western blotting. Cell viability and apoptosis were similarly evaluated by MTT assay and flow cytometry. Results High-risk MDS patients showed significant SHP-1 hypermethylation compared with low-risk patients, and patients with no SHP-1 methylation had longer overall survival. SHP-1 expression was significantly increased at mRNA and protein levels following 5-Aza treatment, while the phosphorylation of STAT3 protein was significantly decreased. Apoptosis increased significantly in MDS cells treated with higher doses of 5-Aza while cell viability decreased significantly. Conclusion SHP-1 hypermethylation was associated with poor prognosis in HR patients with MDS, suggesting it could be used as a prognostic indicator.

GLI1 Inhibitor GANT61 Deregulates stat3 Phosphorylation In Chronic Lymphocytic Leukemia Cells

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4935-4935
Author(s):  
Cheng Wang ◽  
Kang Lu MM ◽  
Xin Wang
Keyword(s):  
Bone Marrow ◽  
Chronic Lymphocytic Leukemia ◽  
Cell Viability ◽  
Signaling Pathway ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Bone Marrow Cells ◽  
Lymphocytic Leukemia ◽  
Stat3 Phosphorylation ◽  
Hh Signaling

Abstract Background Hedgehog(Hh) family has come to be recognized as key fundamental mediators of many carcinomas, but conflicting results exist about its role in chronic lymphocytic leukemia (CLL). Here we examined the effect of GLI inhibitor GANT61 to investigate the role of the Hh-signaling pathway in CLL. Methods and Results We conduct real-time PCR for Hedgehog family members on isolated mononuclear cells from peripheral blood (n=35) and bone marrow cells(n=6) to evaluate the presence of the Hh-signaling pathway in CLL. There's no significant difference between peripheral blood and bone marrow cells in levels of Hh members. Profiling of cognate Hh pathway members revealed reduced expression of three key Hh signaling effectors, Patched, Smoothened (SMOH) and GLI, in peripheral blood mononuclear cells (PBMC), whereas transcription levels of other investigated members(SHH, IHH, DHH, GLI2, GLI3 etc.) resembled normal B-lymphocyte levels. However, we found a great heterogeneity for the expression levels of the Hh family with a subset of about 25% of CLL PBMC samples showing high transcript levels ( 1.5-fold than the median) for GLI1 and SMO. There is a direct positive correlation between GLI1 expression and SMO expression. We performed western-blot in CLL PBMC samples and found a positive correlation between phosphorylation of stat3 and GLI1 (figure 1). We examined the activity of GANT61 on viability of cell lines and primary CLL cells (N=3) in vitro by CCK8. GANT61 reduced the cell viability to 65% ± 14% after 24 hours of culture at concentration of 20uM (mean +/¨C SD, P < 0.05). We found that the capacity of GANT61 to inhibit CLL cell viability was associated with stat3 phosphorylation, which is time and dose dependent (figure 2). Conclusion These results suggest that in CLL Hh pathway is closely related to stat3 pathway. Moreover, these studies reveal a potential mechanism for the anti-leukemia activity of GANT61 which might inhibit viability of CLL cells by deregulating stat3 phosphorylation. Disclosures: No relevant conflicts of interest to declare.

Extensive apoptosis of bone marrow cells as evaluated by the in situ end-labelling (ISEL) technique may be the basis for ineffective haematopoiesis in patients with myelodysplastic syndromes

2009 ◽  
Vol 62 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Agapi Parcharidou ◽  
Azra Raza ◽  
Theofanis Economopoulos ◽  
Efstathios Papageorgiou ◽  
Dimitra Anagnostou ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndromes ◽  
Bone Marrow Cells ◽  
Marrow Cells

Expression of Toll-like receptor 9 in bone marrow cells of myelodysplastic syndromes is down-regulated during transformation to overt leukemia

2010 ◽  
Vol 88 (2) ◽  
pp. 293-298 ◽  
Author(s):  
Nobuo Kuninaka ◽  
Morito Kurata ◽  
Kouhei Yamamoto ◽  
Shiho Suzuki ◽  
Shigeaki Umeda ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndromes ◽  
Bone Marrow Cells ◽  
Toll Like Receptor ◽  
Overt Leukemia ◽  
Marrow Cells

scholarly journals Clinical significance ofTFR2andEPORexpression in bone marrow cells in myelodysplastic syndromes

2016 ◽  
Vol 176 (3) ◽  
pp. 491-495 ◽  
Author(s):  
Augusta Di Savino ◽  
Valentina Gaidano ◽  
Antonietta Palmieri ◽  
Francesca Crasto ◽  
Alessandro Volpengo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Clinical Significance ◽  
Myelodysplastic Syndromes ◽  
Bone Marrow Cells ◽  
Marrow Cells

scholarly journals Fabrication and Biological Analysis of Highly Porous PEEK Bionanocomposites Incorporated with Carbon and Hydroxyapatite Nanoparticles for Biological Applications

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3572
Author(s):  
P. D. Swaminathan ◽  
Md. Nizam Uddin ◽  
P. Wooley ◽  
Ramazan Asmatulu
Keyword(s):  
Bone Marrow ◽  
Cell Viability ◽  
Bone Marrow Cells ◽  
Cell Attachment ◽  
Marrow Cell ◽  
Biological Properties ◽  
Carbon Particles ◽  
Biological Tests ◽  
Carbon Based Nanomaterials ◽  
Highly Porous

Bone regeneration for replacing and repairing damaged and defective bones in the human body has attracted much attention over the last decade. In this research, highly porous polyetheretherketone (PEEK)/hydroxyapatite (HA) bionanocomposite scaffolds reinforced with carbon fiber (CF) and carbon nanotubes (CNTs) were fabricated, and their structural, mechanical, and biological properties were studied in detail. Salt porogen (200–500 µm size) leaching methods were adapted to produce porous PEEK structures with controlled pore size and distribution, facilitating greater cellular infiltration and biological integration of PEEK composites within patient tissue. In biological tests, nanocomposites proved to be non-toxic and have very good cell viability. In addition, bone marrow cell growth was observed, and PEEK/HA biocomposites with carbon particles showed increased cell attachment over the neat PEEK/HA composites. In cell viability tests, bionanocomposites with 0.5 wt% CNTs established good attachment of cells on disks compared to neat PEEK/HA biocomposites. A similar performance was seen in culture tests of bone marrow cells (osteoblasts and osteoclasts). The 0.5 wt% CF for osteoblasts and 1 wt% CNTs for osteoclasts showed higher cell attachment. The addition of carbon-based nanomaterials into PEEK/HA has been identified as an effective approach to improve cell attachment as well as mechanical and biological properties. With confirmed cell attachment and sustained viability and proliferation of the fabricated PEEK/HA/CNTs, CF bionanocomposites were confirmed to possess excellent biocompatibility and will have potential uses in bone scaffolding and other biomedical applications.

Ultrastructural Observations on Bone Marrow Cells of 26 Patients with Myelodysplastic Syndromes

1997 ◽  
Vol 27 (1-2) ◽  
pp. 165-172 ◽  
Author(s):  
Amos M. Cohen ◽  
Svetlana Alexandrova ◽  
Hanna Bessler ◽  
Moshe Mittelman ◽  
Zwi Cycowitz ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndromes ◽  
Bone Marrow Cells ◽  
Marrow Cells

Over-Expression of Cancerous Inhibitor of PP2A (CIP2A) in Bone Marrow Cells from Patients with a Group of High-Risk Myelodysplastic Syndromes

2013 ◽  
Vol 20 (2) ◽  
pp. 399-407 ◽  
Author(s):  
Na Li ◽  
Shinya Abe ◽  
Morito Kurata ◽  
Shiho Abe-Suzuki ◽  
Iichiroh Onishi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Myelodysplastic Syndromes ◽  
Bone Marrow Cells ◽  
Over Expression ◽  
Marrow Cells

Definition of RAEB-I and RAEB-Ii According to the Who Classification of Myelodysplastic Syndromes (MDS): Problems Emerging from a Large Multicenter Registry.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1432-1432
Author(s):  
Alessandro Levis ◽  
L. Godio ◽  
M. Girotto ◽  
M. Bonferroni ◽  
T. Callegari ◽  
...  
Keyword(s):  
Internal Medicine ◽  
Bone Marrow ◽  
Myelodysplastic Syndromes ◽  
Bone Marrow Cells ◽  
Clinical Information ◽  
Bone Marrow Trephine Biopsy ◽  
A Value ◽  
Cd34 Cells ◽  
Definition Of

Abstract BACKGROUND. TheWHO classification of myelodysplastic syndromes (MDS) is based on the evaluation of bone marrow morphology. The two categories of REAB-I and RAEB-II are apparently easy to differentiate on the basis of bone marrow blast percent. However there are no so far data about the differences among cytology, histology and immunophenotypic evaluation of blasts in order to discrimante non-RAEB from RAEB-I and RAEB-II categories. PATIENTS AND METHODS. The Piemonte MDS Registry was born in 1999 thanks to the cooperation of both Haematology and Internal Medicine departments of our region, with the following aims: a) to follow homogeneous guidelines in diagnosis and treatment of MDS; b) to collect epidemiological and clinical information on a large group of patients; c) to cryopreserve bone marrow cells for molecular biology studies. When obtaining an informed consent, data of patients were prospectively centrally recorded through our web site. A retrospective analysis on differences in diagnosing RAEB, comparing conventional cytology on bone marrow smears (CBM), histochemical evaluation of CD34+ cells on bone marrow trephine biopsy (HBM), and cytofluorimetric count of CD34+ and CD117+ cells (IBM) has been done. RESULTS. From June 1999 to December 2003, 633 MDS patients were registered from 37 different institutions: 364 (57%) from haematology and/or academic institutions and 269 (43%) from internal medicine departments of community hospitals. Mean age was 72 (range 23–69). The actual diagnostic distribution of cases according to the WHO criteria based on only morphology evaluation of bone marrow smears was: non-RAEB 429 (68%), RAEB-I 134 (21%), and RAEB-II 70 (11%). Information about the quantification of blasts with both CBM and HBM techniques was avilable in 243 cases. An IBM evaluation was also available in 89 out of this 243 cases. A disagreement between CBM and HBM was evident in 65/243 cases (27%), with HBM over-evaluating and under-evaluating WHO class on the basis of blasts count in 54/243 (22%) and 11/243 cases respectively. When comparing CBM and IBM the disagreement was even higher in 29/89 cases (33%), with IBM over-evaluating blast percent in 9 (10%) and under-evaluating it in 20 cases (23%). The disagreement betwen HBM and IBM was maximum with a value of 39%. The role of CBM in predicting a different prognosis of non-RAEB, RAEB-I and RAEB-II was confirmed. However, when comparing the prognostic value of the three different methods of computing bone marrow blasts, IBM was the best in order to define the good prognostic non-RAEB group. CONCLUSIONS. The distinction among non-RAEB, RAEB-I and RAEB-II is far from beeing highly accurate and reproducible. Important differences are present among CBM, HBM and IBM. While CBM remain the conventional standard system, IBM could offer a tool better and more reproducible than CBM in order to define MDS categories on the basis of blast percentage. A large multicenter study could be useful in order to clarify this point.

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