Analysis of hematopathology and alteration of JAK1/STAT3/STAT5 signaling axis in experimental myelodysplastic syndrome

Daw, Suchismita; Chatterjee, Rahul; Law, Aditya; Law, S.K. Alex

doi:10.1016/j.cbi.2016.10.010

Cited by 12 publications

(12 citation statements)

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“…Altogether, the significant decrease in the neutrophil and few cells appearing as pseudo peldger huet anomalic feature and reductions in WBC total count hinted toward myelodysplasia with reduced number of functional WBC (Figure 1V,VI) 11,41 . In our earlier studies the data emanated from the reticulin stain confirmed the presence of moderate fibrosis in the myelodysplastic bone marrow as compared to the control groups 41 . The scanning electron microscopy revealed noticeable membrane blebbing and disrupted bone marrow cells in myelodysplastic group when compared to control where the cellular architecture was smooth (Figure 1IV).…”

Section: Resultssupporting

confidence: 55%

“…The platelet count was increased in the myelodysplastic peripheral blood when compared to control. Altogether, the significant decrease in the neutrophil and few cells appearing as pseudo peldger huet anomalic feature and reductions in WBC total count hinted toward myelodysplasia with reduced number of functional WBC (Figure 1V,VI) 11,41 . In our earlier studies the data emanated from the reticulin stain confirmed the presence of moderate fibrosis in the myelodysplastic bone marrow as compared to the control groups 41 .…”

Section: Resultssupporting

confidence: 51%

“…The paradoxical expression of specific markers of the bone marrow HSPC's can be associated with the histologic and peripheral blood hemogram results as the H&E stained bone marrow depicted typical infiltration of dysplastic blast cells (Figure 1I,II,V,VI) although there was peripheral blood neutropenia 41,42 . Previously, it was also noted that there was a sharp increase in erythroblast marker CD71 but at the same time blood is anemic lacking functional RBC 41 . The platelet count was increased in the myelodysplastic peripheral blood when compared to control.…”

Section: Resultsmentioning

confidence: 76%

“…N3385) at a dose of 80 mg/kg and kept for 1½ month for proper development of the disease features. The control group of animals received equal volume of 0.9% NaCl 11,12,41‐44 …”

Section: Methodsmentioning

confidence: 99%

“…Mouse model of ENU induced myelodysplasia could be a powerful tool for experimentations as they mimic the human physiology near accuracy. 11,12,[41][42][43][44]…”

mentioning

confidence: 99%

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Quercetin induces autophagy in myelodysplastic bone marrow including hematopoietic stem/progenitor compartment

Daw¹,

Law²

2020

Environmental Toxicology

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Myelodysplastic syndrome (MDS) is regarded as a spectrum of bone marrow failure disorders that share hemato‐pathological state of cellular dysplasia and cytopenia. The modern treatment of cancers like chemotherapy and radiation therapy sometimes severely pounce on the basic hematopoietic stem/progenitor cellular (HSPC) compartment which gradually disclose the clinical symptoms of MDS. The present study involves flowcytometric protein expression analysis of insulin growth factor receptor (IGFR), PI3K‐Akt‐mTOR pathway, the autophagy related proteins (ATG's), the status of antioxidative molecules SOD2 and SDF1 and apoptosis profiling in ethyl‐nitroso‐urea induced myelodysplasia. The redox status that is, reactive oxygen species was estimated with dihydroetidium and the status of mitochondria and lysosomes were checked by Janus green B and neutral red staining respectively, pre and post quercetin treatment in MDS bone marrow. The results revealed the activated IGFR/PI3K/Akt axis in MDS bone marrow but unconventionally both p‐mTOR and autophagy (p‐ATG1, p‐AT6, ATG7, ATG12) was downregulated. Interestingly, post quercetin treatment an upregulation of basal autophagocytosis, reversal of oxidative damage and proper functionality of mitochondria and lysosome was recorded. Taken together, the study hinted that the PI3K‐Akt‐mTOR pathway does not rule over the process of autophagocytosis in HSPC's of MDS bone marrow and the isoflavanoid quercetin remarkably restored autophagocytosis and hematopoietic oxidative status toward normalcy during the progression of myelodysplasia.

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Section: Resultssupporting

confidence: 55%

Section: Resultssupporting

confidence: 51%

Section: Resultsmentioning

confidence: 76%

“…N3385) at a dose of 80 mg/kg and kept for 1½ month for proper development of the disease features. The control group of animals received equal volume of 0.9% NaCl 11,12,41‐44 …”

Section: Methodsmentioning

confidence: 99%

“…Mouse model of ENU induced myelodysplasia could be a powerful tool for experimentations as they mimic the human physiology near accuracy. 11,12,[41][42][43][44]…”

mentioning

confidence: 99%

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Quercetin induces autophagy in myelodysplastic bone marrow including hematopoietic stem/progenitor compartment

Daw¹,

Law²

2020

Environmental Toxicology

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Environmental pollutant N‐N′ethylnitrosourea‐induced leukemic NLRP3 inflammasome activation and its amelioration by Eclipta prostrata and its active compound wedelolactone

Bhattacharyya¹,

Law²

2021

Environmental Toxicology

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Environmental exposure of N‐nitroso compounds (NOCs) from various sources like tobacco smoke, pesticides, smoked meat, and rubber manufacturing industries has been an alarming cause of carcinogenesis. Neonatal exposure to the carcinogenic N‐N′ethylnitrosourea (ENU), a NOC has been established to cause leukemogenesis. Our world is constantly battling against cancer with consistent investigations of new anti‐cancer therapeutics. Plant derived compounds have grasped worldwide attention of researchers for their promising anti‐cancer potentials. Eclipta prostrata is one such ayurvedic herb, renowned for its anti‐inflammatory properties. Currently, it has been explored in various cancer cell lines to establish its anti‐cancer effect, but rarely in in‐vivo cancer models. Wedelolactone (WDL), the major coumestan of E. prostrata is recognized as an inhibitor of IKK, a master regulator of the NF‐kB inflammatory pathway. As persistent inflammation and activated inflammasome contribute to leukemogenesis, we tried to observe anti‐leukemogenic efficacy of E. prostrata and its active compound WDL on the marrow cells of ENU induced experimental leukemic mice. Treatment groups were administered an oral gavage at a dose of 1200 mg/kg and 50 mg/kg b.w of crude extract and WDL respectively for 4 weeks. Various parameters like hemogram, survivability, cytological and histological investigations, migration assay, cell culture, flowcytometry and confocal microscopy were taken into consideration pre‐ and post‐treatment. Interestingly, the plant concoction portrayed maximum effects in comparison to WDL alone. The study suggests E. prostrata and WDL as vital complementary adjuncts for anti‐inflammasome mechanism in ENU‐induced leukemia.

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Homocysteine, Thioretinaco Ozonide, and Oxidative Phosphorylation in Cancer and Aging: A Proposed Clinical Trial Protocol

McCully

2019

Methods in Molecular Biology

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Analysis of hematopathology and alteration of JAK1/STAT3/STAT5 signaling axis in experimental myelodysplastic syndrome

Cited by 12 publications

References 58 publications

Quercetin induces autophagy in myelodysplastic bone marrow including hematopoietic stem/progenitor compartment

Quercetin induces autophagy in myelodysplastic bone marrow including hematopoietic stem/progenitor compartment

Environmental pollutant N‐N′ethylnitrosourea‐induced leukemic NLRP3 inflammasome activation and its amelioration by Eclipta prostrata and its active compound wedelolactone

Homocysteine, Thioretinaco Ozonide, and Oxidative Phosphorylation in Cancer and Aging: A Proposed Clinical Trial Protocol

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