Study on the Burden of Abnormal Hematopoietic Clone of the Patients with Myelodysplastic Syndromes.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4899-4899
Author(s):  
Zonghong Shao ◽  
Huaquan Wang ◽  
Jun Shi ◽  
Yanran Cao ◽  
Hong Liu ◽  
...  

Abstract Background Myelodysplastic syndromes (MDS) is a group of clone haematopoietic stem cell diseases. The burden of abnormal hematopoietic clone plays key roles in the development of this disease and needs to be further studied quantitively. Methods The ratio of the counted bone marrow cells with abnormal chromosomes to the total counted bone marrow cells was regarded as the index of MDS clone burden. The disease severity related parameters including white cell count, hemoglobin, platelet count, lactate dehydrogenase level, bone marrow blast, myeloid differentiation index, the ratio of cFU-GM to CFU-GM, micromegakaryocyte, transfusion, IL-2, TNF, CD4+ and CD8+ T cells of MDS patients were assayed and the correlations between those parameters and MDS clone burden were also analysed. Results The clone burden of MDS patients was (67.4±36.2)%. MDS clone burden correlated positively with bone marrow blasts(r =0.483, P=0.012), negatively with hemoglobin level(r = −0.445, P= 0.023); The number of blasts, hemoglobin and erythocytes in high clone burden(>50%) and low clone burden(≤50%) groups were (7.78±5.51)% and (3.45±3.34)%(P=0.035), (56.06±14.28)g/L and (76.40±24.44)g/L(P=0.013), (1.82±0.12)×1012/L and (2.32±0.21)×1012/L(P=0.034)respectively. CD4+ T lymphcytes of MDS patients and normal controls were (274.18±71.85)×106/L and (454.82±205.88)×106/L(P=0.012)respectively. CD8+ T lymphcytes of MDS patients and normal controls were (240.45±150.01)×106/L an (305.27±145.14)×106/L(P=0.317)respectively. The serum level of interleukin 2 of MDS patients and normal control group were (6.29±3.58)ng/ml and (3.11±1.40)ng/ml (P=0.002) respectively. The serum level of tumor necrosis factor of MDS patients and normal control group were (2.42±1.79)ng/ml and (1.68±0.69)ng/ml(P=0.124)respectively. The ratio of CD4 to CD8 in high clone burden MDS patients was (1.90±0.52), and that in low clone burden patients was (0.97±0.44)(P=0.022). Conclusion The quantitive clonal karyotype abnormalities and deficient T cell immunity are important parameters for evaluating MDS severeity and prediciting it’s progression.

2013 ◽  
Vol 6 (2) ◽  
pp. 77-82 ◽  
Author(s):  
Nazia Nazam ◽  
Mohammad Iqbal Lone ◽  
Sibhghatulla Shaikh ◽  
Waseem Ahmad

Abstract The possible genotoxic activity of Dichlorvos (2,2-Dichlorovinyl-O,O-dimethyl phosphate/DDVP, CAS No. 62-73-7), an organophosphorus insecticide was investigated employing three cytogenetic end points, i.e. micronucleus (MN) assay, mitotic indices (MI) and chromosome abberation (CA) analysis in vivo. The assays were carried out in hematopoietic bone marrow cells of Mus musculus at concentrations of 10, 20 and 30% of LD50 for intraperitoneal (ip) administration, corresponding to 0.06, 0.08 and 0.13 mg/kg Bwt, respectively. The normal control group received single ip dose of distilled water (2 ml/100 g Bwt), while animals of the positive group were injected with cyclophosphamide, a model mutagen (40 mg/kg Bwt) under identical conditions. The animals were sacrificed 24, 48 and 72 hrs post treatment. Under the present experimental conditions, there was no evidence of significant increase of MN frequencies at any dose or sampling time in polychromatic (PCE) and normochromatic (NCE) erythrocytes. The PCE/NCE ratio was not notably affected; however, a slight depression in prolonged exposure (48, 72 hr) intervals and a slight increase at the 24 hr interval were observed. Cells with various structural chromosome aberrations were noted but no significant (p<0.05; Man-Whitney U-test) differences in the frequencies of CA or mitotic indices (p<0.05; X2 test) were observed between Dichlorvos treated groups and the normal control group at doses or time intervals used. The results of the present investigation reflects a negative in vivo genotoxic potential of Dichlorvos at sublethal doses in bone marrow cells. Further studies are underway to confirm the presence or absence of genotoxic activity since compounds negative in genotoxic evaluation are susceptible of being carcinogens triggering cancer by genotoxic or non-genotoxic mechanisms.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4966-4966
Author(s):  
Zonghong Shao ◽  
Lanzhu Yue ◽  
Rong Fu ◽  
Huaquan Wang ◽  
Lijuan Li ◽  
...  

Abstract Abstract 4966 Background Recent studies have shown that interleukin-3 receptor α(CD123) is highly expressed on leukemia stem cells of patients with acute myeloid leukemia, and is correlated with tumor load and poor prognosis. The expression of CD123 may also be high in patients with myelodysplastic syndromes (MDS). In this study, the expression of CD123 as well as granulocyte colony stimulating factor (G-CSF) receptor (CD114) on the bone marrow cells of patients with MDS was investigated in order to explore the molecular marker of the malignant clone of MDS. Methods Forty-two patients with MDS, who were diagnosed in the hematological department of General Hospital of Tianjin Medical University from 2008 to 2009, and twelve normal controls were enrolled in this study. FACS was used to measure the expression of CD123 on CD34+CD38- cells and CD114 on CD34+ cells of the bone marrow of these patients and controls and the clinical significance was analyzed. The expression of CD114 on CD123+CD34+CD38- cells was further measured to explore the molecular marker of the malignant clone in MDS. Results The ratio of CD34+CD38-/CD34+ in the bone marrow cells of MDS patients was [(14.03±5.27)%], significantly higher than that of normal controls [(7.70±4.36)%] (P<0.01); The ratio of CD123+CD34+CD38-/CD34+CD38- in the bone marrow cells of MDS patients[(48.39±28.15)%]was significantly higher than that of normal controls [(8.75±11.71)%] (P<0.01), and was significantly positively correlated with the proportion of bone marrow blasts(r=0.457, P<0.05). The ratio of CD114+CD34+/CD34+ in the bone marrow cells of MDS patients [(33.05±21.71)%] was lower than that of normal controls [(38.99±19.07)%], but with no significance(P>0.05). The expression of CD114 on CD123+CD34+CD38-cells [(34.82±29.58)%] was significantly lower than that on CD123-CD34+CD38-cells [(53.48±27.41)%] of MDS patients (P<0.05). Conclusions MDS patients displayed higher proportion of CD34+CD38-/CD34+ than normal controls. CD123 was highly expressed in the bone marrow of patients with MDS, significantly correlated with the proportion of bone marrow blasts, thus might be the marker of MDS malignant clone. CD123+CD34+CD38-cells exhibited lower expression of G-CSF receptors, which might partly explain why MDS clone responsed worse to G-CSF in vitro and in vivo. Disclosures: No relevant conflicts of interest to declare.


2009 ◽  
Vol 25 (7) ◽  
pp. 467-471 ◽  
Author(s):  
BN Mojidra ◽  
K. Archana ◽  
AK Gautam ◽  
Y. Verma ◽  
BC Lakkad ◽  
...  

Pan masala is commonly consumed in south-east Asian and other oriental countries as an alternate of tobacco chewing and smoking. Genotoxic potential of pan masala (pan masala plain and pan masala with tobacco known as gutkha) was evaluated employing chromosome aberration (CA) and micronucleus (MN) assay in vivo. Animals were exposed to three different doses (0.5%, 1.5% and 3%) of pan masala plain (PMP) and gutkha (PMT) through feed for a period of 6 months and micronucleus and chromosomal aberrations were studied in the bone marrow cells. Induction of mean micronuclei in polychromatic erythrocytes (MNPCE) and normochromatic erythrocyte (MNNCE) was higher in both types of pan masala treated groups with respect to control group. Both pan masala plain and gutkha treatment significantly induced the frequency of MNPCE and MNNCE in the bone marrow cells, indicating the genotoxic potential. Furthermore, slight decline in the ratio of polychromatic erythrocytes to normochromatic erythrocytes was also noticed, suggesting the cytotoxic potential even though the ratio was statistically non significant. A dose-dependent, significant increase in chromosome aberration was observed in both types of pan masala treated mice with respect to control. However, no significant difference in micronucleus and chromosomal aberration induction was noticed between two types of pan masala exposed (PMP and PMT) groups. Results suggest that both types of pan masala, i.e. plain and gutkha, have genotoxic potential.


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

2010 ◽  
Vol 88 (2) ◽  
pp. 293-298 ◽  
Author(s):  
Nobuo Kuninaka ◽  
Morito Kurata ◽  
Kouhei Yamamoto ◽  
Shiho Suzuki ◽  
Shigeaki Umeda ◽  
...  

2016 ◽  
Vol 176 (3) ◽  
pp. 491-495 ◽  
Author(s):  
Augusta Di Savino ◽  
Valentina Gaidano ◽  
Antonietta Palmieri ◽  
Francesca Crasto ◽  
Alessandro Volpengo ◽  
...  

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

2013 ◽  
Vol 20 (2) ◽  
pp. 399-407 ◽  
Author(s):  
Na Li ◽  
Shinya Abe ◽  
Morito Kurata ◽  
Shiho Abe-Suzuki ◽  
Iichiroh Onishi ◽  
...  

2009 ◽  
Vol 2009 ◽  
pp. 1-6 ◽  
Author(s):  
Sahdeo Prasad ◽  
Smita Srivastava ◽  
Madhulika Singh ◽  
Yogeshwer Shukla

Glyphosate (N-(phosphonomethyl) glycine,C3H8NO5P), a herbicide, used to control unwanted annual and perennial plants all over the world. Nevertheless, occupational and environmental exposure to pesticides can pose a threat to nontarget species including human beings. Therefore, in the present study, genotoxic effects of the herbicide glyphosate were analyzed by measuring chromosomal aberrations (CAs) and micronuclei (MN) in bone marrow cells of Swiss albino mice. A single dose of glyphosate was given intraperitoneally (i.p) to the animals at a concentration of 25 and 50 mg/kg b.wt. Animals of positive control group were injectedi.p. benzo(a)pyrene (100 mg/kg b.wt., once only), whereas, animals of control (vehicle) group were injectedi.p. dimethyl sulfoxide (0.2mL). Animals from all the groups were sacrificed at sampling times of 24, 48, and 72 hours and their bone marrow was analyzed for cytogenetic and chromosomal damage. Glyphosate treatment significantly increases CAs and MN induction at both treatments and time compared with the vehicle control (P<.05). The cytotoxic effects of glyphosate were also evident, as observed by significant decrease in mitotic index (MI). The present results indicate that glyphosate is clastogenic and cytotoxic to mouse bone marrow.


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