Genes Involved in Maintaining the Bone Marrow Stroma Are Dysregulated in Patients with Myelofibrosis: Lenalidomide Treatment Up-regulates SOCS3

Anticancer Res. 2015 Oct;35(10):5219-23.

Abstract

Aim: The purpose of the present study was to determine whether genes involved in the organization of the hematopoietic niche were dysregulated in patients with primary myelofibrosis (MF) treated with lenalidomide.

Materials and methods: We used reverse-transcription quantitative polymerase chain reaction to study the expression of a set of genes involved in the organization of the hematopoietic niche in peripheral blood and bone marrow (BM) mononuclear cell (MNC) samples from 32 patients with primary MF who participated in a phase II trial of lenalidomide plus prednisone.

Results: At baseline (before treatment) cyclo-oxygenase 2 (COX2) was significantly up-regulated, while chemokine (C-X-C motif) receptor 4 (CXCR4), paired box 5 (PAX5) C-terminus, and hypoxia inducible factor 1A (HIF1A) were significantly down-regulated in BM MNCs from patients with primary MF compared to BM MNCs from healthy individuals. After 9 months of treatment, the expression of suppressor of cytokine signaling 3 (SOCS3) was significantly increased.

Conclusion: Patients with primary MF showed aberrant expression of several genes involved in maintaining BM homeostasis and our findings suggest that treatment with lenalidomide plus prednisone up-regulates SOCS3.

Keywords: Myelofibrosis; SOCS3; bone marrow stroma; gene expression; lenalidomide.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / therapeutic use
  • Case-Control Studies
  • Clinical Trials, Phase II as Topic
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Lenalidomide
  • Male
  • Middle Aged
  • Prednisone / administration & dosage*
  • Prednisone / pharmacology
  • Primary Myelofibrosis / drug therapy*
  • Primary Myelofibrosis / genetics
  • Primary Myelofibrosis / pathology
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins / genetics*
  • Thalidomide / administration & dosage
  • Thalidomide / analogs & derivatives*
  • Thalidomide / pharmacology

Substances

  • Antineoplastic Agents
  • SOCS3 protein, human
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Thalidomide
  • Lenalidomide
  • Prednisone