Dataset Information

Platelet Proteome in Myeloproliferative Neoplasms

ABSTRACT: Patients with chronic Myeloproliferative Neoplasms (MPN) including polycythaemia vera (PV) and essential thrombocythemia (ET) exhibit unique clinical features, such as a tendency toward thrombosis and hemorrhage, and risk of disease progression to secondary bone marrow fibrosis and/or acute leukemia. Although an increase in blood cell lineage counts (quantitative features) contribute to these morbid sequelae, the significant qualitative abnormalities of myeloid cells that contribute to vascular risk are not well understood. Here, we address this critical knowledge gap via a comprehensive and untargeted profiling (using label free quantitative mass spectrometry) of the platelet proteome in a large (n= 140) cohort of patients (from two independent sites) with an established diagnosis of PV and ET. We discover distinct MPN platelet protein expression and confirm key molecular impairments associated with proteostasis and thrombosis mechanisms of potential relevance to MPN pathology.

INSTRUMENT(S): Bruker Daltonics timsTOF series

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Platelet, Platelet

DISEASE(S): Essential Thrombocythemia,Polycythemia Vera

SUBMITTER: Sarah Kelliher

LAB HEAD: Barry Kevane

PROVIDER: PXD046324 | Pride | 2024-10-17

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	analysis.tdf_bin	Other
	summary_PRIDE.txt	Txt
	uniprot-human_reference_proteom-2022.07.29-13.37.36.57.fasta	Fasta

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Publications

Platelet proteomic profiling reveals potential mediators of immunothrombosis and proteostasis in myeloproliferative neoplasms.

Kelliher Sarah S Gamba Sara S Weiss Luisa L Shen Zhu Z Marchetti Marina M Schieppati Francesca F Scaife Caitriona C Madden Stephen S Bennett Kathleen K Fortune Anne A Maung Su S Fay Michael M Ní Áinle Fionnuala F Maguire Patricia P Falanga Anna A Kevane Barry B Krishnan Anandi A

Blood advances 20240801 16

PMID: 38861353

Similar Datasets

Project description:Myeloproliferative neoplasms (MPN) are clonal hematopoietic diseases that include essential thrombocytosis (ET), polycythemia vera (PV) and primary myelofibrosis (PMF) as well as BCR-ABL+ chronic myelogenous leukemia (CML). In the past several years, studies with cDNA microarrays have defined patterns of gene expression corresponding to specific molecular abnormalities, oncologic phenotypes, and clinical outcomes in hematologic malignancies. This study was aimed at the description of a gene expression signature in MPN which would eventually present a new pathogenetic approaching and also diagnostic as well as prognostic information. Using cDNA microarray analysis, involving 25,100 unique genes, we studied the gene expression profile of the pluripotent hematopoietic CD34+ stem cells and mature granulocytes obtained from peripheral blood of ET, PV, PMF and CML patients compared with healthy individuals. The average number of CD34+ cells (cells/µl) in peripheral blood was approximately 6 in PV and ET, 111 in PMF and 2880 in CML as measured by flow cytometry. A somatic point mutation JAK2V617F was detected in 93% of PV, 73% of PMF and 55% of ET patients within genetically homogenous population. The homozigosity for JAK2V617F mutation was the highest in PV (60%), less prominent in PMF (42%) and low in ET (11%) patients. The JAK2V617F mutation negative patients were also negative for exon 12 mutations. Approximately 420, 680 and 1130 genes had unique expression among CD34+ cells of ET, PV and PMF patients, respectively. In addition comparing to healthy controls, ET, PV, PMF and CML patients showed difference in 840, 1180, 1160 and 2050 expressed genes, respectively. Furthermore, we studied EPO and JAK-STAT signaling pathways related genes expression in MPN. The FOS, RAF1 and JAK2 gene expression, related to EPO signaling pathway, was elevated in ET, PV, PMF and reduced in CML comparing to healthy controls. Related to these genes, the JAK2V617F mutation homozygous and heterozygous patients generally displayed more significant differences comparing to patients with no mutation. STAT5 gene expression was decreased in all MPN patients. CSF3R, STAT1 and STAT3 gene expression, related to JAK-STAT signaling pathway, was elevated in ET, PV, PMF and reduced in CML comparing to healthy controls. CREBBP gene expression was reduced in CD34+ cells of ET, PV and PMF patients, but during maturation it enhanced expression in granulocytes. In conclusion, molecular profiling of CD34+ cells and granulocytes revealed a certain number of genes with changed expression that, beyond their recognized function in disease pathogenesis, can be related to patients’ clinical characteristics and may have an imminent prognostic relevance.