Immunoproteasome Genes Are Modulated in CD34<sup>+</sup> JAK2<sup>V617F</sup> Mutated Cells from Primary Myelofibrosis Patients

oleh: Michelino Di Rosa, Cesarina Giallongo, Alessandra Romano, Daniele Tibullo, Giovanni Li Volti, Giuseppe Musumeci, Ignazio Barbagallo, Rosa Imbesi, Paola Castrogiovanni, Giuseppe A. Palumbo

Format: Article
Diterbitkan: MDPI AG 2020-04-01

Deskripsi

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<sup>+</sup> cells from peripheral blood (PB) of PMF patients. Therefore, we merged two microarray datasets of healthy control subjects and PMF (34 JAK2<sup>V617F</sup> MUTATED and 28 JAK2 wild-type). The GO analysis of upregulated genes revealed enrichment for JAK2/STAT1 pathway gene set in PB CD34<sup>+</sup> cells of PMF patients with and without the <i>JAK2<sup>V617F</sup> mutation</i> comparing to the healthy control subjects, and in particular a significant upregulation of immunoproteasome (IP)-belonging genes as <i>PSMB8</i>, <i>PSMB9,</i> and <i>PSMB10.</i> A more detailed investigation of the IFN-gamma (IFNG) pathway also revealed that <i>IFNG, IRF1,</i> and <i>IFNGR2</i> were significantly upregulated in PB CD34<sup>+</sup> cells of PMF patients carrying the mutation for JAK2<sup>V617F</sup> compared to JAK2 wild-type PMF patients. Finally, we showed an upregulation of HLA-class I genes in PB CD34<sup>+</sup> cells from PMF JAK2<sup>V617F</sup> 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 <i>JAK2<sup>V617F</sup> mutation</i>.