TLR4 and RAGE conversely mediate pro-inflammatory S100A8/9-mediated inhibition of proliferation-linked signaling in myeloproliferative neoplasms

ConclusionsFrom our data we conclude that the S100A8 and S100A9 granulocyte and plasma levels are increased in MPN patients, along with inflammation markers, depending on theirJAK2V617F mutation allele burden. We also found that S100A8/9-mediated inhibition of the proliferation-related AKT and ERK1/2 signaling pathways can be decreased byCALR mutation-dependent TLR4 blocking and increased by RAGE inhibition in MPN.
Source: Cellular Oncology - Category: Cancer & Oncology Source Type: research

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Publication date: Available online 7 December 2019Source: Best Practice &Research Clinical HaematologyAuthor(s): Mrinal M. Patnaik
Source: Best Practice and Research Clinical Haematology - Category: Hematology Source Type: research
Publication date: Available online 6 December 2019Source: Best Practice &Research Clinical HaematologyAuthor(s): Rory M. Shallis, Amer M. ZeidanAbstractThe clinicopathology of MDS and MPN are not mutually exclusive and for this reason the category of myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) exists. Several sub-entities have been included under the MDS/MPN umbrella, including MDS/MPN-unclassifiable (MDS/MPN-U) for those cases whose morphologic and clinical phenotype do not meet criteria to be classified as any other MDS/MPN sub-entity. Though potentially regarded as a wastebasket diagnosis, since i...
Source: Best Practice and Research Clinical Haematology - Category: Hematology Source Type: research
Publication date: Available online 6 December 2019Source: Best Practice &Research Clinical HaematologyAuthor(s): Terra LashoAbstractAtypical chronic myeloid leukemia is an esoteric myeloid malignancy with features of both myeloproliferative and myelodysplastic syndromes. This disease is characterized primarily by morphologic-based criteria, and has clinical and molecular features overlapping with other myeloid malignancies. No one molecular abnormality is specific, and multiple mutations are often present in various combinations, due to the malignant multi-step clonal evolution of myeloid malignancies. In this review, ...
Source: Best Practice and Research Clinical Haematology - Category: Hematology Source Type: research
Authors: Stein BL, Martin K Abstract Thrombotic and hemorrhagic complications are prevalent in patients with essential thrombocythemia, polycythemia vera, and myelofibrosis. Given the impact on morbidity and mortality, reducing the risk of thrombosis and/or hemorrhage is a major therapeutic goal. Historically, patients have been risk stratified on the basis of traditional factors, such as advanced age and thrombosis history. However, multiple factors contribute to the thrombotic tendency, including gender, mutational profile, inflammatory stress, and abnormal cell adhesion. Management includes cardiovascular risk r...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
This article reviews the successes and limitations of JAK-STAT inhibition, surveys the strategies behind emerging therapies, and discusses the challenges that are present in moving beyond JAK-STAT. PMID: 31808852 [PubMed - in process]
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
Authors: McMullin MF Abstract In the patient presenting with an elevated blood count who does not have an acquired clonal disorder causing a myeloproliferative neoplasm, hereditary erythrocytosis or hereditary thrombocytosis needs to be considered as a possible explanation. A young patient and/or those with a family history of myeloproliferative neoplasm should specifically raise this possibility. Among the causes of hereditary erythrocytosis are mutations in the genes in the oxygen sensing pathway and high-affinity hemoglobins. Hereditary thrombocytosis has been shown to be accounted for by mutations in THPO, MPL,...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
CONCLUSIONS Bioinformatics analysis identified DEGs and hub genes that interacted with CD34+ cells and neutrophils that may predict an increased risk of thrombosis in patients with ET. These preliminary findings should be validated using next-generation sequencing (NGS) and clinical studies. PMID: 31801935 [PubMed - in process]
Source: Medical Science Monitor - Category: Research Tags: Med Sci Monit Source Type: research
In conclusion, AURKA, BORA and PLK1 are involved in pathogenesis of myelofibrosis and may affect survival. Future studies investigating these interesting associations are warranted.
Source: Blood Cells, Molecules, and Diseases - Category: Hematology Source Type: research
Publication date: Available online 3 December 2019Source: Best Practice &Research Clinical HaematologyAuthor(s): Kristen B. McCullough, Mrinal M. PatnaikAbstractOptimal treatment for myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) overlap syndromes remain to be defined and are currently extrapolated from MDS and MPN. The heterogeneity of these diseases and their rare occurrences add to this void. Supportive care therapies such as erythropoiesis stimulating agents, iron chelation and cytoreductive therapy do not have prospective evidence in these disorders and the only approved treatments, hypomethylating...
Source: Best Practice and Research Clinical Haematology - Category: Hematology Source Type: research
Contributors : Yu-Lin Su ; Xiuli Wang ; Mati Mann ; Tomasz Adamus ; Dayson Moreira ; Dongfang Wang ; Zhuoran Zhang ; Ching Ouyang ; Xin He ; Bin Zhang ; Piotr Swiderski ; Stephen Forman ; David Baltimore ; Ling Li ; Guido Marcucci ; Mark Boldin ; Marcin KortylewskiSeries Type : Expression profiling by RT-PCROrganism : Mus musculusNF- κB is a key regulator of inflammation and cancer progression, with important role in leukemogenesis. Despite therapeutic potential, targeting NF-κB using pharmacologic inhibitors proved challenging. Here, we describe a myeloid cell-selective NF-κB inhibitor using miR146a mimi...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by RT-PCR Mus musculus Source Type: research
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