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Description of the microRNA repertoire of leucocytes of patients suffering from atypical myeloproliferative syndromes

ABSTRACT: Atypical Myeloproliferative Neoplasms (aMPN) share characteristics of MPN and Myelodysplastic Syndromes (MDS). Although anomalies of tyrosine-kinases or proteins involved in cytokine signaling are common in MPN, the pathophysiology of atypical MPN is still elusive. Since deregulation of microRNAs has been involved in the biology of various cancers, we screened the miRNome of aMPN compared to CML or reactive hyperleukocytosis (RHL) states. The study highligths the overexpression of miR-10a in the aMPN group

ORGANISM(S): Homo sapiens

PROVIDER: GSE75666 | GEO | 2017/12/01

SECONDARY ACCESSION(S): PRJNA305008

REPOSITORIES: GEO

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Description of the microRNA repertoire of leucocytes of patients suffering from atypical myeloproliferative syndromes

Project description:Atypical Myeloproliferative Neoplasms (aMPN) share characteristics of MPN and Myelodysplastic Syndromes (MDS). Although anomalies of tyrosine-kinases or proteins involved in cytokine signaling are common in MPN, the pathophysiology of atypical MPN is still elusive. Since deregulation of microRNAs has been involved in the biology of various cancers, we screened the miRNome of aMPN compared to CML or reactive hyperleukocytosis (RHL) states. The study highligths the overexpression of miR-10a in the aMPN group We analysed the microRNA repertoire of blood leukocyte RNA from patients with aMPN (n=16), CML (n=10) or reactive hyperleukocytosis (n=4)

2016-09-01 | E-GEOD-75666 | biostudies-arrayexpress

Targeting CHAF1B enhances interferon activity in myeloproliferative neoplasms

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Pbx1 expression is required for myeloproliferative neoplasm onset and maintenance

Project description:Pre B cell leukemia homeobox 1 (Pbx1) regulates the balance between self-renewal and differentiation of hematopoietic stem cells, and maintains proto-oncogenic transcriptional pathways implicated in several tumors. Its aberrant expression was found in a subset of myeloproliferative neoplasms (MPN) patients bearing the JAK2V617F mutation. To investigate if Pbx1 contributes to MPN, and to explore its potential as therapeutic target, we generated a new mouse strain, that we called JP, by crossing a known JAK2V617F inducible knock-in MPN model with a Pbx1 conditional-ko. In JP mice we can simultaneously activate the human JAK2 mutation and delete Pbx1. Typical MPN features, such as thrombocytemia and granulocytosis, did not develop in the absence of Pbx1. Erythrocytosis, initially displayed by JP mice, gradually resolved over time. Moreover, splenic myeloid metaplasia and in vitro cytokine independent growth were rescued by Pbx1 inactivation. Through RNA-Sequencing we analyzed molecular pathways downstream of Pbx1 and involved in MPN maintenance in stem and progenitor cells. The aberrant transcriptome in the MPN model compared to wild-type was rescued by the absence of Pbx1. Our results demonstrate that inhibition of the Pbx1-driven transcriptional program is beneficial in MPN. Modulation of Pbx1 activity by direct targeting or by targeting its downstream mediators might thus represent a novel therapeutic approach.

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Expression of Autophagy Genes in Myeloproliferative Disorders

Project description:Comparison of ATG gene family members in MPN pattients with normal controls

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Gene expression of MYB wild type and MYB knockdown myeloproliferative K11bL cells

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2021-09-20 | GSE120639 | GEO

Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis [MPN patients]

Project description:We used expression profiling, SNP arrays, and mutational profiling to investigate a well-characterized cohort of MPN patients. MPN patients with homozygous JAK2V617F mutations were characterized by a distinctive transcriptional profile. Notably, a transcriptional signature consistent with activated JAK2 signaling is seen in all MPN patients regardless of clinical phenotype or mutational status. In addition, the activated JAK2 signature was present in patients with somatic CALR mutations. Conversely, we identified a gene expression signature of CALR mutations; this signature was significantly enriched in JAK2-mutant MPN patients consistent with a shared mechanism of transformation by JAK2 and CALR mutations. We also identified a transcriptional signature of TET2 mutations in MPN patent samples. Our data indicate that MPN patients, regardless of diagnosis or JAK mutational status are characterized by a distinct gene expression signature with upregulation of JAK-STAT target genes, demonstrating the central importance of the JAK-STAT pathway in MPN pathogenesis. [MPN patients] We have performed microarray gene expression analysis in 93 patients with MPNs (28 PV, 47 ET, 18 MF) and 11 age-matched normal donors.

2014-06-03 | E-GEOD-54644 | biostudies-arrayexpress

A Unique Signaling Feedback Circuit Defines Interferon Responses in Myeloproliferative Neoplasms

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2022-01-10 | PXD021748 | Pride

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