Cytokine Expression Pattern in Bone Marrow Microenvironment after Allogeneic Stem Cell Transplantation in Primary Myelofibrosis

Biol Blood Marrow Transplant. 2016 Apr;22(4):644-650. doi: 10.1016/j.bbmt.2015.12.006. Epub 2015 Dec 19.

Abstract

The only curative therapy for primary myelofibrosis (PMF) is allogeneic stem cell transplantation (ASCT). However, although we know that patients can benefit from ASCT, we do not know the extent of the changes of the expression profile of cytokines and matrix modulation factors. In this first systematic analysis, we evaluated the expression profile of 103 factors before and after transplantation to identify potential biomarkers. The expression of fibrosis-, inflammation-, and angiogenesis-associated genes was analyzed in a total of 52 bone marrow biopsies: PMF patients (n = 14) before and after ASCT and, for control purposes, post-ASCT multiple myeloma patients (n = 14) and non-neoplastic hematopoiesis (n = 10). In post-ASCT PMF cases, decreased expression of tissue inhibitor of metalloproteinases (TIMP) and platelet-derived growth factor alpha (PDGFA) correlated with bone marrow remodeling and hematological remission. Expression of several other matrix factors remained at high levels and may contribute to post-ASCT remodeling. This is the first systematic analysis of cytokine expression in post-ASCT PMF bone marrow that shows that normalization of bone marrow microenvironment is paralleled by decreased expression of TIMP and PDGFA.

Keywords: Allogeneic stem cell transplantation; Fibrosis; Primary myelofibrosis (PMF).

MeSH terms

  • Adult
  • Aged
  • Bone Marrow / immunology
  • Bone Marrow / pathology
  • Case-Control Studies
  • Cellular Microenvironment / immunology*
  • Cytokines / genetics
  • Cytokines / immunology*
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / immunology
  • Female
  • Gene Expression Regulation
  • Hematopoiesis / immunology
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Male
  • Middle Aged
  • Multiple Myeloma / genetics
  • Multiple Myeloma / immunology*
  • Multiple Myeloma / pathology
  • Multiple Myeloma / therapy
  • Platelet-Derived Growth Factor / genetics
  • Platelet-Derived Growth Factor / immunology*
  • Primary Myelofibrosis / genetics
  • Primary Myelofibrosis / immunology*
  • Primary Myelofibrosis / pathology
  • Primary Myelofibrosis / therapy
  • Retrospective Studies
  • Tissue Inhibitor of Metalloproteinases / genetics
  • Tissue Inhibitor of Metalloproteinases / immunology*
  • Transplantation, Homologous

Substances

  • Cytokines
  • Extracellular Matrix Proteins
  • Platelet-Derived Growth Factor
  • Tissue Inhibitor of Metalloproteinases
  • platelet-derived growth factor A