miR-155 promotes FLT3-ITD–induced myeloproliferative disease through inhibition of the interferon response

Wallace, Jared; Kagele, Dominique; Eiring, Anna M.; Kim, Carissa N.; Hu, Ruiming; Runtsch, Marah C.; Alexander, Margaret; Huffaker, Thomas B.; Lee, Soh Hyun; Patel, Ami B.; Mosbruger, Timothy; Voth, Warren P.; Rao, Dinesh S.; Miles, Rodney R.; Round, June L.; Deininger, Michael W.; O’Connell, Ryan M.

doi:10.1182/blood-2016-09-740209

Cited by 59 publications

(48 citation statements)

References 36 publications

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“…97 This was in contrast to miR-155 high levels (.10fold above control), in which miR-155 acted as a tumor suppressor by repressing colony formation and proliferation, establishing a dosedependent effect of miR-155 in these AML mouse models. The study did confirm that the intermediate miR-155 expression levels were a better representation of what was seen in their pediatric AML data set (increased ;oneto sevenfold), values that were consistent with miR-155 expression in other AML data sets, 12,45 suggesting that miR-155 likely has a predominately oncogenic effect in human AML. The study highlights the importance of considering the level of expression in various model systems when studying miRNAs in AML.…”

Section: Varying Levels Of Mirna Expression May Have Opposing Effectsmentioning

confidence: 60%

“…miR-155 seems to have no phenotypic effect in MLL-rearranged AML, 44 but it is consistently found to play an oncogenic role in FLT3-ITD-driven AML pathogenesis. 42,45 miR-126 plays different roles and regulates different targets in normal vs malignant hematopoietic stem cells 35 and, interestingly, both overexpression and knockout of miR-126 promote leukemogenesis. 34 These studies highlight how the influence of an miRNA in AML can be dependent on the underlying genetic abnormalities that drive disease or cell type of expression.…”

Section: Improper Regulation Of Inflammatory Pathways Leads To Amlmentioning

confidence: 99%

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MicroRNAs and acute myeloid leukemia: therapeutic implications and emerging concepts

Wallace

O’Connell

2017

Blood

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158

129

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Acute myeloid leukemia (AML) is a deadly hematologic malignancy characterized by the uncontrolled growth of immature myeloid cells. Over the past several decades, we have learned a tremendous amount regarding the genetic aberrations that govern disease development in AML. Among these are genes that encode noncoding RNAs, including the microRNA (miRNA) family. miRNAs are evolutionarily conserved small noncoding RNAs that display important physiological effects through their posttranscriptional regulation of messenger RNA targets. Over the past decade, studies have identified miRNAs as playing a role in nearly all aspects of AML disease development, including cellular proliferation, survival, and differentiation. These observations have led to the study of miRNAs as biomarkers of disease, and efforts to therapeutically manipulate miRNAs to improve disease outcome in AML are ongoing. Although much has been learned regarding the importance of miRNAs in AML disease initiation and progression, there are many unanswered questions and emerging facets of miRNA biology that add complexity to their roles in AML. Moving forward, answers to these questions will provide a greater level of understanding of miRNA biology and critical insights into the many translational applications for these small regulatory RNAs in AML.

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Section: Varying Levels Of Mirna Expression May Have Opposing Effectsmentioning

confidence: 60%

Section: Improper Regulation Of Inflammatory Pathways Leads To Amlmentioning

confidence: 99%

MicroRNAs and acute myeloid leukemia: therapeutic implications and emerging concepts

Wallace

O’Connell

2017

Blood

Self Cite

158

129

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“…In addition, researchers have found that miR-155-5p mediates T lymphocyte differentiation [26] and inhibits cell apoptosis [27]. In pathogenesis, miR-155-5p is associated with many diseases, such as cancer [28,29], cardiovascular disease [30], autoimmune disease [31], metabolic disease [32], and neurological disorders [33]. During HSV-1 infection, several studies have shown that the expression level of miR-155-5p is markedly increased by the viral infection [34,35].…”

Section: Introductionmentioning

confidence: 99%

MiR-155-5p modulates HSV-1 replication via the epigenetic regulation of SRSF2 gene expression

Wang

et al. 2019

Epigenetics

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A previous study reported that miR-155-5p knockout mice were more resistant to herpes simplex virus type I (HSV-1) infection. However, the exact underlying molecular mechanism remains to be elucidated. Here, we demonstrated that HSV-1 infection upregulates miR-155-5p expression. By binding to the promoter of serine/arginine-rich splicing factor 2 (SRSF2), which is an important transcriptional activator of HSV-1 genes that was previously reported by our group, and altering the histone modification located near the transcription start site (TSS) of the SRSF2 gene, miR-155-5p promotes the transcription of the SRSF2 gene, ultimately increasing viral replication and viral gene expression. Our results provide insight for an understanding of the roles and molecular mechanism of miR-155-5p in HSV-1 replication and the epigenetic control of SRSF2 gene expression.

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“…Many genetic abnormalities linked to AML have been identified during the past few decades. 25 Among these abnormalities; the micro-RNA family has been given increased attention, especially over the past ten years. Clear evidence suggests that miRNAs play a role in many aspects of AML development, including maintenance of hematopoietic stem cells, growth, proliferation, differentiation, and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Low expression of miR‐204 is associated with expression of CD34 and poor performance status in denovo AML

Abdelhafiz

El-Sayed

Saber

et al. 2020

Int J Lab Hematology

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AML is the most common type of acute leukemia in adults, accounting for approximately 80% of adult cases of acute leukemia. 1 AML is generally recognized as disease of late age, with first-time diagnoses of AML made at 68 years of age on average. 2 Still, children account for 6% to 7% of cases of AML and have a biology that is quite different from that of adult patients. 3The disease arises from bone marrow stem cells which proliferate uncontrollably with impaired differentiation capacity, leading Abstract Introduction: Acute myeloid leukemia (AML) is the most common acute leukemia in adults. There is growing evidence that microRNAs (miRNAs) provide prognostic information in AML. MiR-204 has a tumor suppressor function, and several studies have proven its role in solid cancers. The aim of this work is to evaluate the level of expression of miR-204 in adults newly diagnosed with AML with normal karyotype and to correlate its level of expression with disease outcome and different prognostic factors. Patients and methods: The study included 87 adult patients newly diagnosed with AML. Detection of miR-204 was done using RT-PCR in patients and seven agematched controls. Results: Acute myeloid leukemia patients showed significantly lower miR-204 expression, compared to control group (P = .029). Low miR-204 expression was significantly associated with positive CD34 (P = .017), with poor performance status (PS) (P = .009), and with the presence of diabetes mellitus (DM) (P = .014). Low expression of miR-204 was also significantly associated with shorter overall survival (OS) (P = .020) and disease-free survival (DFS) (P = .013). Low miR-204 expression was identified as an independent prognostic factor for prediction of shorter OS (P = .034) and DFS (P = .027) in AML. Conclusion: To the best of our knowledge; this is the first time to prove the correlation between miR-204 expression and CD34 expression. Further study of this correlation is needed to confirm the role of miR-204 in CD34-positive cells, including leukemic stem cells. This correlation may have therapeutic implications. MiR-204 can be used as a biomarker for PS in AML patients. K E Y W O R D S acute myeloid leukemia, CD34, leukemic stem cells, miR-204, performance status S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Abdelhafiz AS, Elsayed GM, Saber MM, Gameel A, Hamdy N. Low expression of miR-204 is associated with expression of CD34 and poor performance status in denovo AML. Int J Lab Hematol. 2020;42:263-269.

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miR-155 promotes FLT3-ITD–induced myeloproliferative disease through inhibition of the interferon response

Abstract: • miR-155 promotes myeloproliferation in the bone marrow, spleen, and blood of mice carrying the FLT3-ITD mutation.• miR-155 suppresses the IFN response in FLT3-ITD

Cited by 59 publications

References 36 publications

MicroRNAs and acute myeloid leukemia: therapeutic implications and emerging concepts

MicroRNAs and acute myeloid leukemia: therapeutic implications and emerging concepts

MiR-155-5p modulates HSV-1 replication via the epigenetic regulation of SRSF2 gene expression

Low expression of miR‐204 is associated with expression of CD34 and poor performance status in denovo AML

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