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Article

Immunoproteasome Genes Are Modulated in CD34+ JAK2V617F Mutated Cells from Primary Myelofibrosis Patients

1
Department of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, 95125 Catania, Italy
2
Department of Medical, Surgical Sciences and Advanced Technologies “G.F. Ingrassia”, University of Catania, 95125 Catania, Italy
3
Division of Hematology, A.O.U. Policlinic-OVE, University of Catania, 95122 Catania, Italy
4
Department of Biomedical and Biotechnological Sciences, Medical Biochemistry Section, University of Catania, 95125 Catania, Italy
5
Research Center on Motor Activities (CRAM), University of Catania, 95125 Catania, Italy
6
Department of Drug Science, Biochemistry Section, University of Catania, 95125 Catania, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(8), 2926; https://doi.org/10.3390/ijms21082926
Received: 28 February 2020 / Revised: 17 April 2020 / Accepted: 20 April 2020 / Published: 22 April 2020
(This article belongs to the Special Issue BCR-ABL1 Negative Myeloproliferative Neoplasms)
Primary myelofibrosis (PMF) is a rare myeloproliferative neoplasm characterized by stem-cell-derived clonal over-proliferation of mature myeloid lineages, bone marrow fibrosis, osteosclerosis, defective erythropoiesis, and pro-inflammatory cytokine over-expression. The aim of the present study was to highlight possible differences in the transcriptome among CD34+ cells from peripheral blood (PB) of PMF patients. Therefore, we merged two microarray datasets of healthy control subjects and PMF (34 JAK2V617F MUTATED and 28 JAK2 wild-type). The GO analysis of upregulated genes revealed enrichment for JAK2/STAT1 pathway gene set in PB CD34+ cells of PMF patients with and without the JAK2V617F mutation comparing to the healthy control subjects, and in particular a significant upregulation of immunoproteasome (IP)-belonging genes as PSMB8, PSMB9, and PSMB10. A more detailed investigation of the IFN-gamma (IFNG) pathway also revealed that IFNG, IRF1, and IFNGR2 were significantly upregulated in PB CD34+ cells of PMF patients carrying the mutation for JAK2V617F compared to JAK2 wild-type PMF patients. Finally, we showed an upregulation of HLA-class I genes in PB CD34+ cells from PMF JAK2V617F mutated patients compared to JAK2 wild-type and healthy controls. In conclusion, our results demonstrate that IPs and IFNG pathways could be involved in PMF disease and in particular in patients carrying the JAK2V617F mutation. View Full-Text
Keywords: immunoproteasome; JAK2V617F; primary myelofibrosis; bioinformatics; CD34+ cells; HLA-class I; innate immunity immunoproteasome; JAK2V617F; primary myelofibrosis; bioinformatics; CD34+ cells; HLA-class I; innate immunity
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MDPI and ACS Style

Di Rosa, M.; Giallongo, C.; Romano, A.; Tibullo, D.; Li Volti, G.; Musumeci, G.; Barbagallo, I.; Imbesi, R.; Castrogiovanni, P.; Palumbo, G.A. Immunoproteasome Genes Are Modulated in CD34+ JAK2V617F Mutated Cells from Primary Myelofibrosis Patients. Int. J. Mol. Sci. 2020, 21, 2926. https://doi.org/10.3390/ijms21082926

AMA Style

Di Rosa M, Giallongo C, Romano A, Tibullo D, Li Volti G, Musumeci G, Barbagallo I, Imbesi R, Castrogiovanni P, Palumbo GA. Immunoproteasome Genes Are Modulated in CD34+ JAK2V617F Mutated Cells from Primary Myelofibrosis Patients. International Journal of Molecular Sciences. 2020; 21(8):2926. https://doi.org/10.3390/ijms21082926

Chicago/Turabian Style

Di Rosa, Michelino, Cesarina Giallongo, Alessandra Romano, Daniele Tibullo, Giovanni Li Volti, Giuseppe Musumeci, Ignazio Barbagallo, Rosa Imbesi, Paola Castrogiovanni, and Giuseppe A. Palumbo 2020. "Immunoproteasome Genes Are Modulated in CD34+ JAK2V617F Mutated Cells from Primary Myelofibrosis Patients" International Journal of Molecular Sciences 21, no. 8: 2926. https://doi.org/10.3390/ijms21082926

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