Flaming and fanning: The Spectrum of inflammatory influences in myelodysplastic syndromes

Banerjee, Titas; Calvi, Laura M.; Becker, Michael W.; Liesveld, Jane L.

doi:10.1016/j.blre.2019.04.004

Cited by 44 publications

(36 citation statements)

References 149 publications

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“…Cell pyroptosis death is found to be a potential toxic effect of xenobiotic pollutants that results in over-activation of inflammation, tissue damage, even malignant tumors [1,6,27]. It was reported pyroptosis is a highly inflammatory form of programmed cell death drove by caspases activation accompanied with release of pro-inflammatory cytokines IL1β [18].…”

Section: Discussionmentioning

confidence: 99%

“…Limit studies have shown that pyroptosis may be involved in multiple types of haematological diseases such as MDS and acute myelogenous leukemia (AML). For example, researcher found that pyroptotic and other cellular inflammatory mediators promoted progression of MDS [1]. Rodriguez-Cimadevilla JC, et al, has reported that IL1β can stimulate AML growth [21].…”

Section: Introductionmentioning

confidence: 99%

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Benzene metabolites trigger pyroptosis and contribute to haematotoxicity via TET2 directly regulating the Aim2/Casp1 pathway

et al. 2019

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BackgroundLong term low-dose benzene exposure leads to the inhibition of haematopoiesis. However, the underlying mechanisms remained poorly defined, especially mediated by early effector molecules.MethodsHere, we first found in mRNA microarray that pyroptotic classic genes (Casp1, 4, 5, and IL1β) were up-regulated and represented dose-dependent differential expression in controls, low-dose benzene-exposed and chronic benzene-poisoned workers, and the expression of Casp1 and IL1β were confirmed in low-dose benzene-exposed workers and was accompanied with elevated potent proinflammatory IL1β. In vitro studies showed that benzene metabolites induced AHH-1 cell pyroptosis through activating Aim2/Casp1 pathway with the increased expression of GSDMD. Meanwhile, TET2 overexpression was elevated in vivo and in vitro and it was positively correlated with IL1β. Further, we verified that pyroptosis caused by 1,4-BQ could be ameliorated in vitro by RNAi or pretreatment with Dimethyloxalylglycine (DMOG), the inhibitor of TET2.FindingsExposure to benzene can trigger pyroptosis via TET2 directly regulating the Aim2/Casp1 signaling pathway to cause haematotoxicity.InterpretationBenzene metabolites induced pyroptotic cell death through activation of the Aim2/Casp1 pathway which can be regulated by Tet2 overexpression. Tet2 may be a potential risk factor and is implicated in the development of benzene-related diseases.FundNational Natural Science Foundation of China; the Support Project of High–level Teachers in Beijing Municipal Universities in the Period of 13th Five–year Plan; Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Benzene metabolites trigger pyroptosis and contribute to haematotoxicity via TET2 directly regulating the Aim2/Casp1 pathway

et al. 2019

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“…For example, sterile inflammation via NLRP3 inflammasome activation has been linked to LR MDS. Activation of NLRP3 triggered bone marrow inflammation, expansion of myeloid-derived suppressor cells in the bone marrow, and a higher rate of hematopoietic cell damage and cell death [ 105 , 106 ]. Since then, it has been widely accepted that NLRP3-driven pyroptosis, a caspase-1 dependent proinflammatory form of lytic cell death, is fundamental in MDS pathology.…”

Section: Aspects On Iron Hepcidin Inflammation and Mdsmentioning

confidence: 99%

EnvIRONmental Aspects in Myelodysplastic Syndrome

Petzer

Theurl

Weiss

et al. 2021

IJMS

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Systemic iron overload is multifactorial in patients suffering from myelodysplastic syndrome (MDS). Disease-immanent ineffective erythropoiesis together with chronic red blood cell transfusion represent the main underlying reasons. However, like the genetic heterogeneity of MDS, iron homeostasis is also diverse in different MDS subtypes and can no longer be generalized. While a certain amount of iron and reactive oxygen species (ROS) are indispensable for proper hematological output, both are harmful if present in excess. Consequently, iron overload has been increasingly recognized as an important player in MDS, which is worth paying attention to. This review focuses on iron- and ROS-mediated effects in the bone marrow niche, their implications for hematopoiesis and their yet unclear involvement in clonal evolution. Moreover, we provide recent insights into hepcidin regulation in MDS and its interaction between erythropoiesis and inflammation. Based on Tet methylcytosine dioxygenase 2 (TET2), representing one of the most frequently mutated genes in MDS, leading to disturbances in both iron homeostasis and hematopoiesis, we highlight that different genetic alteration may have different implications and that a comprehensive workup is needed for a complete understanding and development of future therapies.

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“…Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis, leading to hematopoietic precursor cell apoptosis and peripheral blood cytopenia [1]. In MDS, cytogenetic aberrations play an important role in classi cation and prognostication.…”

Section: Introductionmentioning

confidence: 99%

Multiplex ligation-dependent probe amplification identifies copy number changes in normal and undetectable karyotype MDS patients

Ma¹,

Wang

et al. 2020

Preprint

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Background In myelodysplastic syndromes (MDS), cytogenetic aberrations play an important role for classification and prognostication. However, more than 50% low risk MDS patients harbor a normal karyotype. Recently, multiplex ligation-dependent probe amplification (MLPA) has emerged as an effective and robust method for the detection of cytogenetic aberrations in MDS patients.Methods To characterize the subset of MDS with normal karyotype or failed chromosome banding analysis, we analyzed 144 patient samples with normal karyotype or undetectable through regular chromosome banding, which were subjected to parallel comparison via fluorescence in situ hybridization (FISH) and MLPA.Results MLPA identifies copy number changes in 16.7% of 144 MDS patients and we observed a significant difference in overall survival (OS) (median OS: undefined vs 27 months, p=0.0071) in patients with normal karyotype proved by MLPA, versus aberrant karyotype cohort as determined by MLPA. Interestingly, patients with undetectable karyotype via regular chromosome banding indicated inferior outcome. Conclusion Collectively, MDS patients with normal or undetectable karyotype via chromosome banding analysis can be further clarified by MLPA, providing more prognostic information that benefit for individualized therapy.

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Flaming and fanning: The Spectrum of inflammatory influences in myelodysplastic syndromes

Cited by 44 publications

References 149 publications

Benzene metabolites trigger pyroptosis and contribute to haematotoxicity via TET2 directly regulating the Aim2/Casp1 pathway

Benzene metabolites trigger pyroptosis and contribute to haematotoxicity via TET2 directly regulating the Aim2/Casp1 pathway

EnvIRONmental Aspects in Myelodysplastic Syndrome

Multiplex ligation-dependent probe amplification identifies copy number changes in normal and undetectable karyotype MDS patients

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