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Precision medicine in myelodysplastic syndromes
Published in Debmalya Barh, Precision Medicine in Cancers and Non-Communicable Diseases, 2018
While CSNK1A1 is the CRL4CRBN target in del(5q) MDS, CRL4CRBN targets in lower risk non-del(5q) remain to be determined. The mechanism of action of lenalidomide is still unclear in non-del(5q) MDS cells. Recent evidence shows that lenalidomide directly improves erythropoietin receptor (EPOR) signaling by EPOR upregulation mediated by a posttranscriptional mechanism (Basiorka et al., 2016a). Lenalidomide stabilizes the EPOR protein by inhibition of the E3 ubiquitin ligase RNF41 (ring finger protein 41, also known as neuregulin receptor degradation protein-1 [Nrdp1] and fetal liver ring finger [FLRF]) (Basiorka et al., 2016a) and induces lipid raft assembly to enhance EPOR signaling in MDS erythroid progenitors (McGraw et al., 2012, 2014).
Case 66
Published in Atul B. Mehta, Keith Gomez, Clinical Haematology, 2017
PRV or PPP. Familial polycythaemia can arise due to mutations in the erythropoietin receptor. Mutations in genes which result in increased activity of hypoxia inducible factors (HIFs) will increase erythropoietin production. Familial polycythaemia can result from a mutation in the von Hippel-Lindau gene (VHL) (so called ‘Chuvash polycythaemia’) and mutations in the PHD2 gene have a similar effect. Mutations of HIF2 alpha can increase erythropoietin production to cause familial polycythaemia.
Zidovudine
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Catherine L. Cherry, Suzanne M. Crowe
The mechanism by which zidovudine causes macrocytosis and anemia is not completely understood. Vitamin B12 is not typically altered, and red cell folate is unchanged or even increased (Richman et al., 1987a; Baum et al., 1991). Serum erythropoietin levels are increased in people receiving zidovudine (Spivak et al., 1989), but the bone marrow appears to be refractory to its effects (Spivak et al., 1989; Gallicchio and Hughes, 1993). A possible explanation for this is that zidovudine down-regulates erythropoietin receptor expression on bone marrow progenitor cells (Gogu et al., 1992).
Red blood cell distribution width at admission predicts outcome in critically ill patients with kidney failure: a retrospective cohort study based on the MIMIC-IV database
Published in Renal Failure, 2022
Rongqian Hua, Xuefang Liu, Enwu Yuan
Regarding the underlying mechanisms between higher RDW levels and elevated all-cause mortality of patients with kidney failure, malnutrition, systemic inflammation, and oxidative stress (OS) have been proposed as possible etiologies. First, malnutrition is known to increase RDW, which is common in patients on dialysis in terms of dialysis-induced nutrient losses and the implementation of a low protein diet [34,35]. Second, inflammation inhibits iron metabolism and the hematopoietic function of bone marrow. Research has confirmed that proinflammatory cytokines can downregulate the expression of erythropoietin receptor and thereby inhibit erythropoietin-induced RBC maturation and proliferation 36,37, which is related to increased RDW. Finally, increased heterogeneity of RBCs might result from OS [38,39]. OS is present even in the early stages and is further exacerbated by dialysis due to contact with the dialysis membrane via blood, low levels of vitamins C and E, reduced selenium levels, and decreased activity of the glutathione system [40]. Altogether, it is probable that patients with kidney failure would have elevated levels of RDW. In our study, we confirmed that a higher RDW level was associated with all-cause mortality after adjusting for potential confounders.
Maternal plasma levels of vitamin D in postterm pregnancy
Published in Journal of Obstetrics and Gynaecology, 2022
Kadriye Erdoğan, Nazlı Tunca Sanlier, Bülent Çelik, Burak Arslan, Gülşah Diktaş, Özge Yücel Çelik, Caner Köse, Yaprak Engin-Üstün
Anaemia and vitamin D deficiency are two important public health problems that can accompany many acute and chronic diseases. Our results are in agreement with the studies suggesting that vitamin D deficiency is associated with anaemia since vitamin D is a strong regulator of hepcidin ferroportin (Smith et al. 2017). 1,25-dihydroxy vitamin D reduces hepcidin mRNA levels by binding to the Vitamin D receptor in vitro (Bacchetta et al. 2014). In another in vitro study conducted in bone marrow red cells, it was shown that calcitriol increased erythropoietin receptor expression and stimulated proliferation synergistically with erythropoietin (Alon et al. 2002). It has been suggested that vitamin D has a role in down-regulating both proinflammatory cytokines and hepcidin (Smith and Tangpricha 2015). It was reported that cholecalciferol supplementation would improve anaemia by modulating pro- and anti-inflammatory cytokines, leading to a decrease in hepcidin levels and improvement of anaemia (Silva and Faustino 2015).
Targeting on glycosylation of mutant FLT3 in acute myeloid leukemia
Published in Hematology, 2019
Statins act by blocking 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoA reductase) [79] which play an important role in the mevalonate pathway that generates dolichol related to N-linked glycosylation [80]. Statins could inhibit proliferation of cancer cells in vitro and in vivo [81–84]. Mevastatin can increase the sensitivity of patients with primary AML to standard therapy [81]; Simvastatin increases the toxicity of chemotherapeutic drugs to colorectal cancer cells [82]; Lovastatin can inhibit the expression of erythropoietin receptor by double inhibition of glycation [85]. Erythropoietin (EPO) is essential for erythroid progenitor cells to survive by interacting with cell surface receptors. Recent literatures have shown that erythropoietin receptor (EPOR) is expressed in many cancer cells. Erythropoietin (EPO) that a member of the class I cytokine family is synthesized into 62 kDa precursors and glycosylated into 64 kDa proteins. The mature EpoR has 66 kDa molecular weight and complex Golgi-processed glycosylation mode [86]. The mature EpoR in fully glycosylated state can be blocked by Lovastatin to prevent surface expression of EpoR [85]. In addition, insulin and insulin-like growth factor (IGF) signaling occurs when intracellular receptor is under proper N-glycosylation of polyphenols. Especially at that time, statins significantly reduced the proliferation induced by IGF and insulin. Statins treatment resulted in the decreased expression of receptor membrane receptor, suggesting the destruction of glycation-dependent division [87].