A proteomic study of myeloproliferative neoplasms using reverse-phase protein arrays

Leuk Lymphoma. 2020 Dec;61(13):3052-3065. doi: 10.1080/10428194.2020.1805110. Epub 2020 Aug 15.

Abstract

Myeloproliferative neoplasms polycythemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis constitute a group of haematological diseases. The comprehensive assessment of signaling pathway activation in blood cells may aid the understanding of MPN pathophysiology. Thus, levels of post-translational protein modifications and total protein expression were determined in MPN patients and control leukocytes by using reverse-phase protein arrays (RPPA). Compared to control samples, p-SRC, p-CTNNB1, c-MYC, MCL-1, p-MDM2, BAX and CCNB1 showed higher expression in PV samples than controls. P-JAK2/JAK2 and pro-apoptotic BIM showed differential expression between JAK2V617F-positive and -negative ET patients. Apoptosis, cancer and PI3K/AKT pathways proteins showed differential expression among the studied groups. For most of the proteins analyzed using Western-Blot and RPPA, RPPA showed higher sensitivity to detect subtle differences. Taken together, our data indicate deregulated protein expression in MPN patients compared to controls. Thus, RPPA may be a useful method for broad proteome analysis in MPN patients´ leukocytes.

Keywords: JAK2 mutation; Myeloproliferative neoplasms; cell signaling pathways; global protein expression; reverse-phase protein array.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Janus Kinase 2 / genetics
  • Mutation
  • Myeloproliferative Disorders* / diagnosis
  • Myeloproliferative Disorders* / genetics
  • Neoplasms*
  • Phosphatidylinositol 3-Kinases
  • Protein Array Analysis
  • Proteomics

Substances

  • Janus Kinase 2