title: Genes Involved in Maintaining the Bone Marrow Stroma Are Dysregulated in Patients with Myelofibrosis: Lenalidomide Treatment Up-regulates SOCS3.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Molecular Diagnostics and Genetics, Department of Laboratory Diagnosis, Dubrava University Hospital, Zagreb, Croatia.
authors.forename: Ana
authors.initials: A
authors.lastname: Livun
authors.affiliation: Department of Leukemia, The University of MD Anderson Cancer Center, Houston, TX, U.S.A.
authors.forename: Kate J
authors.initials: KJ
authors.lastname: Newberry
authors.affiliation: Department of Leukemia, The University of MD Anderson Cancer Center, Houston, TX, U.S.A.
authors.forename: Taghi
authors.initials: T
authors.lastname: Manshouri
authors.affiliation: University of Zagreb, School of Medicine, Zagreb, Croatia.
authors.forename: Rajko
authors.initials: R
authors.lastname: Kusec
authors.affiliation: Department of Leukemia, The University of MD Anderson Cancer Center, Houston, TX, U.S.A. sverstov@mdanderson.org.
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D016022:Case-Control Studies; D017322:Clinical Trials, Phase II as Topic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage* / Q000494:pharmacology; D055728:Primary Myelofibrosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D013792:Thalidomide; D000077269:Lenalidomide; D011241:Prednisone
keywords: Myelofibrosis; SOCS3; bone marrow stroma; gene expression; lenalidomide