Role of some members of chemokine/cytokine network in the pathogenesis of thalassemia and sickle cell hemoglobinopathies: a mini review

Mousavi, Zahra; Yazdani, Zinat; Moradabadi, Alireza; Hoseinpourkasgari, Fatemeh; Hassanshahi, Gholamhossein

doi:10.1186/s40164-019-0145-x

Cited by 13 publications

(8 citation statements)

References 48 publications

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“…This activation is achieved by the PlGF-VEGFR-1 interaction and involves the PI-3 kinase/AKT and ERK-1/2 signaling pathways ( 335 ). Because VOC in SCD is promoted by inflammation and leukocyte adhesion stimulated by cytokines ( 197 , 336 , 337 ), antibody neutralization of PlGF was tried successfully for reduction of inflammation and vaso-occlusive complications in murine SCD models ( 317 ). Regulation of PlGF levels could also be achieved by manipulating factors that control its transcriptional or translational expression.…”

Section: Hemolysis Plgf and Complications Of Sickle Cell Diseasementioning

confidence: 99%

The Worst Things in Life are Free: The Role of Free Heme in Sickle Cell Disease

Gbotosho¹,

Kapetanaki

Kato

2021

Front. Immunol.

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Hemolysis is a pathological feature of several diseases of diverse etiology such as hereditary anemias, malaria, and sepsis. A major complication of hemolysis involves the release of large quantities of hemoglobin into the blood circulation and the subsequent generation of harmful metabolites like labile heme. Protective mechanisms like haptoglobin-hemoglobin and hemopexin-heme binding, and heme oxygenase-1 enzymatic degradation of heme limit the toxicity of the hemolysis-related molecules. The capacity of these protective systems is exceeded in hemolytic diseases, resulting in high residual levels of hemolysis products in the circulation, which pose a great oxidative and proinflammatory risk. Sickle cell disease (SCD) features a prominent hemolytic anemia which impacts the phenotypic variability and disease severity. Not only is circulating heme a potent oxidative molecule, but it can act as an erythrocytic danger-associated molecular pattern (eDAMP) molecule which contributes to a proinflammatory state, promoting sickle complications such as vaso-occlusion and acute lung injury. Exposure to extracellular heme in SCD can also augment the expression of placental growth factor (PlGF) and interleukin-6 (IL-6), with important consequences to enthothelin-1 (ET-1) secretion and pulmonary hypertension, and potentially the development of renal and cardiac dysfunction. This review focuses on heme-induced mechanisms that are implicated in disease pathways, mainly in SCD. A special emphasis is given to heme-induced PlGF and IL-6 related mechanisms and their role in SCD disease progression.

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Section: Hemolysis Plgf and Complications Of Sickle Cell Diseasementioning

confidence: 99%

The Worst Things in Life are Free: The Role of Free Heme in Sickle Cell Disease

Gbotosho¹,

Kapetanaki

Kato

2021

Front. Immunol.

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“…The CXCL12 signaling pathway plays a key role within cross-talk of the leukemic cells and BM microenvironment interactions. 7,16 To perform its activities, CXCL12 attaches to two namely receptors, CXCR4 and CXCR7 and further transduces on the mTOR pathway in pancreatic and gastric cancers, T cell leukemia, and the human renal cancer cells. Additionally, as described earlier in the text, chemokines are a superfamily of chemoattractant proteins that induce cytoskeletal rearrangement for firm adhesion to specific cells and directional migration.…”

Section: Downstream Signaling Pathways Activated By Cxcl12/cxcr4 7 Imentioning

confidence: 99%

“…Hence, this is of particular relevance to consider that chemokine receptors are extensively expressed by several normal as well as malignant non-leukocyte cell types. [3][4][5][6][7][8] Despite the sensitivity to chemotherapy, the long-term disease-free survival in AML sufferers remained low and it was reported that the majority of the patients most often enter the relapse phase from minimal residual disease (MRD). 9 BM is one of the main locations for MRD where the adhesion of AML cells to the BM components may provide protection from the chemotherapy reagents.…”

Section: Introductionmentioning

confidence: 99%

<p>Significance of CXCL12/CXCR4 Ligand/Receptor Axis in Various Aspects of Acute Myeloid Leukemia</p>

Yazdani¹,

Mousavi²,

Moradabadi³

et al. 2020

CMAR

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Acute myeloid leukemia (AML) is defined as an aggressive disorder which is described by accumulation of immature malignant cells into the bone marrow. Chemokinereceptor axes are defined as factors involved in AML pathogenesis and prognosis. The chemokine receptor CXCR4 along with its ligand, CXCL12 fit in important players that are actively involved in the cross-talk between leukemia cells and bone marrow microenvironment. Therefore, according to the above introductory comments, in this review article, we have focused on delineating some parts played by CXCL12/CXCR4 axis in various aspects of AML malignancy. Targeting both leukemic and stromal cell interaction is nowadays accepted as a wide and attractive strategy for improving the outcome of treatment in AML in a non-cell autonomous manner. This strategy might be employed in a wide variety of AML patients regardless of their causative mutations. In addition to several potential targets involved in the disruption of malignant leukemic cells from their specific protective niches, compounds which interfere with CXCL12/CXCR4 axis have also been explored in multiple early-phase established clinical trials. Moreover, extensive research programs are exploring novel leading mechanisms for leukemia-stromal interactions that appear to find out novel therapeutic targets within the near future.

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“…Thalassaemia is caused by inherited autosomal recessive abnormalities in haemoglobin synthesis [1]. These abnormalities result in an imbalanced production of whole alpha‐ or beta‐globin chains, leading to the formation of defective haemoglobin molecules in both alpha‐ and beta‐thalassaemia, respectively [2]. Depending on the clinical severity and haemoglobin levels, thalassaemia patients may require regular packed red blood cell transfusions with iron chelation therapy, splenectomy or bone marrow transplantation in selected cases.…”

Section: Introductionmentioning

confidence: 99%

Amlodipine as adjuvant therapy to current chelating agents for reducing iron overload in thalassaemia major: a systematic review, meta‐analysis and simulation of future studies

Elfaituri

Ghozy

Ebied³

et al. 2021

Vox Sanguinis

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Background and Objectives Iron overload in thalassaemia is a crucial prognostic factor and a major cause of death due to heart failure or arrhythmia. Therefore, previous research has recommended amlodipine as an auxiliary treatment to current chelating agents for reducing iron overload in thalassaemia patients. Materials and Methods A systematic review and meta‐analysis of the results of three randomized clinical trials evaluating the use of amlodipine in thalassaemia patients through 12 databases were carried out. Results Our final cohort included 130 patients. Insignificant difference in decreasing liver iron concentrations was found between amlodipine and control groups {weighted mean difference = −0·2, [95% confidence interval = (−0·55–0·15), P = 0·26]}. As regards serum ferritin, our analysis also showed no significant difference in serum ferritin between amlodipine and control groups {weighted mean difference [95% confidence interval = −0·16 (−0·51–0·19), P = 0·36]}. Similarly, there was insignificant difference in cardiac T2* between amlodipine and control groups {weighted mean difference [95% confidence interval = 0·34 (−0·01–0·69), P = 0·06]}. Conclusions Despite the growing evidence supporting the role of amlodipine in reducing iron overload in thalassaemia patients, our meta‐analysis did not find that evidence collectively significant. The results of our simulation suggest that when more data are available, a meta‐analysis with more randomized clinical trials could provide more conclusive insights.

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Role of some members of chemokine/cytokine network in the pathogenesis of thalassemia and sickle cell hemoglobinopathies: a mini review

Cited by 13 publications

References 48 publications

The Worst Things in Life are Free: The Role of Free Heme in Sickle Cell Disease

The Worst Things in Life are Free: The Role of Free Heme in Sickle Cell Disease

<p>Significance of CXCL12/CXCR4 Ligand/Receptor Axis in Various Aspects of Acute Myeloid Leukemia</p>

Amlodipine as adjuvant therapy to current chelating agents for reducing iron overload in thalassaemia major: a systematic review, meta‐analysis and simulation of future studies

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