Imatinib mesylate has an inhibitory effect on hematopoiesis in a mice model

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5568-5568
Author(s):  
Jie yu Ye ◽  
Su yi Li ◽  
En yu Liang ◽  
Fan yi Meng ◽  
Beng Chong ◽  
...  

Abstract Imatinib mesylate (Gleevec or STI-571), a tyrosine kinase inhibitor, can potently block both platelet-derived growth factor (PDGF) receptor-α and β by inhibiting the receptor tyrosine kinase activity. Imatinib mesylate has been successfully used to treat patients with chronic myeloid leukemia (CML) and Ph positive acute lymphoid leukemia (ALL). However, a significant number of patients with imatinib mesylate treatment have developed neutropenia, thrombocytopenia and anemia (van Deventer, Hall et al. 2002). Our previous studies have demonstrated that PDGF/PDGFR plays an important role on thrombopoiesis, and blockage of PDGFR by imatinib inhibited the downstream signal pathway, which led to reduce of megakaryocyte production (Ye, et al. Haematologica, 2010). This may partially explain the imatinib-related thrombocytopenia. However, the role of imatinib on normal hematopoiesis remains to be investigated. In the present study, we identified the expression of PDGFR-β on the human megakaryoblastic cells: Meg-01, CHRF-288-11, Dami and M-07e, human erythromyeloblastoid leukemia cells: K-562 and human myeloblastic cells: HL-60 by RT-PCR, western blot and flow cytometry. We then demonstrated the effect of imatinib on normal hematopoiesis in the 8 wk old C57BL/6 mice model. Gleevec (25 mg/kg/day) dissolved in distilled water or water only were given orally for up to 2 wks. 15ul whole blood was taken from postorbital weekly to perform blood cell counts. The Gleevec -treated group showed a reduction of platelet count as compared to the control at day 14 (543.3±71.95×109/L vs. 330.0±62.23×109/L, n=5, P<0.05). Similarly, Gleevec caused a significant decrease in the number of white blood cells on day 14 (9.667×±0.8511×109/L vs. 6.080±0.8015×109/L, n=5, P<0.05). While no significant differences were found on red blood cell count between Gleevec and control groups. The mice bone marrow was harvested from each group to perform CFU assays. Gleevec significantly inhibited the formation of bone marrow CFU-MK (15.33±1.764 vs 3.333±0.6667, n=3), and CFU-GM(13.50±2.784 vs 6.333±0.7265, n=3) compared with the control. There were no significant differences found in CFU-GEMM and CFU/BFU-E formation between the Gleevec and control treatment. Our studies suggested that PDGFR were expressed on hematopoietic cells. Imatinib mesylate, an inhibitor of PDGFR, not only played an important role in malignant hematopoiesis, but also in normal hematopoiesis. Administration of Gleevec reduced white blood cells and megakaryocytes/platelets production, which implied its potential therapeutic role in treating myeloproliferative diseases, such as Essential Thrombocytosis. Disclosures: No relevant conflicts of interest to declare.

2017 ◽  
Vol 24 (04) ◽  
pp. 612-616
Author(s):  
Faisal Irshad ◽  
Hina Mawani ◽  
Sana Naz

Objectives: To determine the effects of Allium sativum essential oil (ASEO)phytotherapy on serum triglycerides, total cholesterol, HDLc, LDLc and blood cell counts inalbino rat model. Study design: Experimental study. Setting and Duration: Animal House,Sindh Agriculture University and Isra University Hyderabad from May 2014 to January 2015.Materials and Methods: 60 albino rats were divided into four groups. Controls were givenPlacebo. Experimental rat groups were given ASEO 100 mg/kg, 200 mg/kg and 300 mg/kgorally for 30 days. Cardiac puncture was performed for blood sampling. Research variableswere analyzed on Statistix 10.0 (USA). Results: Blood lipids showed significant reduction invarious blood lipid fractions. Serum LDLc exhibited with a concomitant rise in serum HDLc (p=0.0001) in high ASEO treated rats. Red blood cells, white blood cells and platelet showedsignificant improvement ASEO fed rats (p=0.001). Conclusion: Allium sativum essential oil(ASEO) phytotherapy showed a rise in HDLc and a reduction in LDLc, triglycerides and totalcholesterol with improvement in red blood cell counts.


2020 ◽  
Vol 8 (1) ◽  
pp. 55-64
Author(s):  
Bestoon T. Mustafa ◽  
Sardar P. Yaba ◽  
Asaad H. Ismail

This study was undertaken to investigate the influence of a homogenous and uniform static magnetic field (SMF) on the main blood cell counts in vitro experiment. Fresh blood samples were collected from albino rats and exposed to SMF (2.4, 6, 25, 50, 75, and 100 mT) versus 15–60 min. Results showed a significant change of blood counts under the low field effects. A 2.4 mT was a trend of white blood cells (WBCs) count increase non-linearly. However, a 6 mT exposure reduced WBCs with about 39%. Other variations fluctuated within 30%. The 25 mT decreased red blood cells (RBCs), hemoglobin, and hematocrit levels with 13% similarly. The lower exposure field, (2.4 and 6) mT, and effects on RBCs were 6% fluctuation. The 6 mT reduced platelet counts with half in comparison to control blood samples. About 20% increase obtained due to 50 mT exposure during all period. None of 75 and 100 mT exposures dominated blood counts alterations. The quiet magnetic field exposure for a certain time can be interesting to control blood cell count-related diseases.


1994 ◽  
Vol 80 (4) ◽  
pp. 306-308 ◽  
Author(s):  
Vayalil Praveenkumar ◽  
Ramadasan Kuttan ◽  
Girija Kuttan

Aims and backgrond Mylosuppression has been found to be one of the major drawbacks in cancer chemotherapy. Presently the effect of Rasayanas, an indigenous herbal drug preparation having immunomodulatory activity, in reducing myelosuppression and subseguent leukopenia was studied. Methods Animals were injected cyclophosphamide (50 mg/kg b.wt. daily for 14 days) with or without Rasayanas (50 mg/animal) and total white blood cells, bone marrow cellularity and survival of the animals were determined. Results Oral administration of Brahma Rasayana (BR) and Ashwagandha/Rasayana (AR) was found to protect mice from cyclophosphamide induced leukopenia. Total white blood cell counts in BR and AR treated animals on day 12 were 3800 and 3000 cells(mm3 respectively, which was significantly high compared to that of controls (700 cells/mm3). When the treatment was stopped on day 14 the value increased to 27,000 and 26,000 cells/mm3. The bone marrow cellularity were also significantly high in BR and AR treated animals (3.45 × 106 and 2.38 × 16 cells femur respectively) compared to that of controls. (0.72 × 106 cells/femur). Conclusion The results indicate the usefulness of Rasayanas in chemotherapy induced myelosuppression and leukopenia.


2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 291-292
Author(s):  
Elle Rottman ◽  
Alisun N Watson ◽  
Catherine Buck ◽  
Tsungcheng Tsai ◽  
Jeffery J Chewning ◽  
...  

Abstract Complete blood cell counts have been used as a diagnostic tool across many animal species including swine. To investigate the factors that cause variation in complete blood cell count results, a total of 2,284 whole blood samples were collected from 2012 to 2019 in preweaning piglets (n = 518), nursery pigs (n = 1,704), and grower pigs (n = 60). Whole blood was collected into K2EDTA blood collection tubes and assayed using an automatic hematologic analyzer within 6 hours of collection. Data were analyzed by Mixed procedure of SAS with gender, parity group, and farrowing season as fixed effects. Body weight and age of pigs served as covariances. Farrowing season was grouped into summer (born during May to October) or winter (or November to April). Pigs that were born from first, second, and third parity, and four and above parity sows were assorted into parity group 1, 2 to 3, and 4+, respectively. Barrows had a greater concentration of total white blood cells (P &lt; 0.01), lymphocytes (P &lt; 0.01), and neutrophils (P &lt; 0.01) compared to gilts. Barrows had lower mean corpuscular volume (P = 0.03), mean corpuscular hemoglobin (P &lt; 0.01), and mean corpuscular hemoglobin concentration (P = 0.02) compared to gilts. Pigs that were farrowed in the winter season had a greater concentration of white blood cells (P = 0.01), neutrophils (P = 0.01), and the percentage of neutrophils (P = 0.03), but were lower in the percentage of lymphocytes (P = 0.03) compared to pigs farrowed during summer. Pigs born to parity four and above sows obtained a greater lymphocyte count (P = 0.01), percentage of neutrophils (P = 0.02), and percentage of lymphocytes (P = 0.01). We concluded that peripheral complete blood cells count results were affected by gender, farrowing season, and sow parity.


BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Cristina Menni ◽  
Panayiotis Louca ◽  
Sarah E. Berry ◽  
Amrita Vijay ◽  
Stuart Astbury ◽  
...  

Abstract Background Chronic inflammation, which can be modulated by diet, is linked to high white blood cell counts and correlates with higher cardiometabolic risk and risk of more severe infections, as in the case of COVID-19. Methods Here, we assessed the association between white blood cell profile (lymphocytes, basophils, eosinophils, neutrophils, monocytes and total white blood cells) as markers of chronic inflammation, habitual diet and gut microbiome composition (determined by sequencing of the 16S RNA) in 986 healthy individuals from the PREDICT-1 nutritional intervention study. We then investigated whether the gut microbiome mediates part of the benefits of vegetable intake on lymphocyte counts. Results Higher levels of white blood cells, lymphocytes and basophils were all significantly correlated with lower habitual intake of vegetables, with vegetable intake explaining between 3.59 and 6.58% of variation in white blood cells after adjusting for covariates and multiple testing using false discovery rate (q < 0.1). No such association was seen with fruit intake. A mediation analysis found that 20.00% of the effect of vegetable intake on lymphocyte counts was mediated by one bacterial genus, Collinsella, known to increase with the intake of processed foods and previously associated with fatty liver disease. We further correlated white blood cells to other inflammatory markers including IL6 and GlycA, fasting and post-prandial glucose levels and found a significant relationship between inflammation and diet. Conclusion A habitual diet high in vegetables, but not fruits, is linked to a lower inflammatory profile for white blood cells, and a fifth of the effect is mediated by the genus Collinsella. Trial registration The ClinicalTrials.gov registration identifier is NCT03479866.


2001 ◽  
Vol 125 (3) ◽  
pp. 391-396 ◽  
Author(s):  
Katharina Ruzicka ◽  
Mario Veitl ◽  
Renate Thalhammer-Scherrer ◽  
Ilse Schwarzinger

Abstract Context.—The new hematology analyzer Sysmex XE-2100 (TOA Medical Electronics, Kobe, Japan) has a novel, combined, white blood cell differential technology and a special reagent system to enumerate nucleated red blood cells. Design.—Performance evaluation of both technologies of the Sysmex XE-2100 according to the H20-A protocol of the National Committee for Clinical and Laboratory Standards and comparison of the results with those for the hematology analyzer Sysmex NE-8000 (TOA Medical Electronics). Specimens.—Five hundred forty-four blood samples randomly chosen from various inpatient and outpatient departments of the Vienna University hospital. Results.—Five-part white blood cell differential counts on the XE-2100 revealed excellent correlation with the manual reference method for neutrophils, lymphocytes, and eosinophils (r = .925, .922, and .877, respectively) and good correlation for monocytes and basophils (r = .756 and .763, respectively). The efficiency rates of flagging for the presence of ≥1% abnormal white blood cells were 83% (XE-2100) and 66% (NE-8000). The correlation of automated and microscopic nucleated red blood cell counts was excellent (r = .97). Conclusions.—From the present evaluation and our former experience with other types of Sysmex analyzers, we conclude that the new white blood cell differential technology of the XE-2100 represents a further development toward more efficient flagging of abnormal white blood cells.


2020 ◽  
Author(s):  
Tiancheng Xia ◽  
Richard Fu ◽  
Nanlin Jin ◽  
Paul Chazot ◽  
Plamen Angelov ◽  
...  

Microscopic blood cell analysis is an important methodology for medical diagnosis, and complete blood cell counts (CBCs) are one of the routine tests operated in hospitals. Results of the CBCs include amounts of red blood cells, white blood cells and platelets in a unit blood sample. It is possible to diagnose diseases such as anemia when the numbers or shapes of red blood cells become abnormal. The percentage of white blood cells is one of the important indicators of many severe illnesses such as infection and cancer. The amounts of platelets are decreased when the patient suffers hemophilia. Doctors often use these as criteria to monitor the general health conditions and recovery stages of the patients in the hospital. However, many hospitals are relying on expensive hematology analyzers to perform these tests, and these procedures are often time consuming. There is a huge demand for an automated, fast and easily used CBCs method in order to avoid redundant procedures and minimize patients’ burden on costs of healthcare. In this research, we investigate a new CBC detection method by using deep neural networks, and discuss state of the art machine learning methods in order to meet the medical usage requirements. The approach we applied in this work is based on YOLOv3 algorithm, and our experimental results show the applied deep learning algorithms have a great potential for CBCs tests, promising for deployment of deep learning methods into microfluidic point-of-care medical devices. As a case of study, we applied our blood cell detector to the blood samples of COVID-19 patients, where blood cell clots are a typical symptom of COVID-19.


Blood ◽  
2003 ◽  
Vol 101 (8) ◽  
pp. 2990-2995 ◽  
Author(s):  
Tetsuo Mitsui ◽  
Sumiko Watanabe ◽  
Yoshihiro Taniguchi ◽  
Sachiyo Hanada ◽  
Yasuhiro Ebihara ◽  
...  

Abstract Severe congenital neutropenia (SCN) is a hematopoietic disorder characterized by neutropenia in peripheral blood and maturation arrest of neutrophil precursors in bone marrow. Patients with SCN may evolve to have myelodysplastic syndrome or acute myelocytic leukemia. In approximately 20% of SCN cases, a truncation mutation is found in the cytoplasmic region of the granulocyte colony-stimulating factor receptor (G-CSFR). We then generated mice carrying murine wild-type G-CSFR and its mutants equivalent to truncations at amino acids 718 and 731 in human G-CSFR, those were reported to be related to leukemic transformation of SCN. Although numbers of peripheral white blood cells, red blood cells, and platelets did not differ among mutant and wild-type G-CSFR transgenic (Tg) mice, both of the mutant receptor Tg mice had one third of peripheral neutrophil cell counts compared with wild-type receptor Tg mice. The mutant receptor Tg mice also showed impaired resistance to the infection with Staphylococcus aureus. Moreover, bone marrow of these Tg mice had an increased percentage of immature myeloid cells, a feature of SCN. This maturation arrest was also observed in in vitro cultures of bone marrow cells of truncated G-CSFR Tg mice under G-CSF stimulation. In addition, clonal culture of bone marrow cells of the truncated G-CSFR Tg mice showed the hypersensitivity to G-CSF in myeloid progenitors. Our Tg mice may be useful in the analysis of the role of truncated G-CSFR in SCN pathobiology.


2021 ◽  
Vol 9 (A) ◽  
pp. 324-327
Author(s):  
Dwi Eni Danarsih ◽  
Pramudji Hastuti ◽  
Agus Kristianto

BACKGROUND: Obesity is a risk factor for cardiovascular disease. Obesity can trigger inflammation by increasing the synthesis of interleukin-6 (IL-6) which leads to leukocyte recruitment, differentiation of B lymphocytes, activating T lymphocyte cells, and triggering hematopoiesis. Variations in the IL-6 promoter gene are known to affect transcription rates. The previous studies have still found different results regarding the relationship between these gene variations and blood cell numbers. AIM: This study aimed to determine the influence of IL-6 gene variation with white blood cells counts in obese people of Indonesia. METHODS: A total of 148 people participated in this cross-sectional study. The number of obese people was 80 subjects and there were 68 non-obese people as controls. Obesity was determined based on the criteria of Asians. RESULTS: Genotype CC was not found in this study, while the GC genotype was found only in the obese group. The GG genotype in obese group had waist circumference, diastolic blood pressure, and higher lymphocyte rates significantly higher than the non-obese group (p < 0.05). CONCLUSIONS: Variation of −174G>C IL-6 gene is associated with high white blood cell counts, especially lymphocytes number in obese people in Indonesia.


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