title: The expression of CXCR4 is down-regulated on the CD34+ cells of patients with myelofibrosis with myeloid metaplasia.
abstract: OBJECTIVE
  We studied the expression of the chemokine receptor CXCR4 on circulating CD34+ cells of patients with myelofibrosis with myeloid metaplasia (MMM), and examined its relationship to the severity of disease.
  
  
  METHODS
  Surface and intracellular CXCR4 expression were measured flow cytometrically in 84 consecutive MMM patients, 16 patients with polycythemia vera (PV), and 20 healthy subjects. In 23 MMM patients, CXCR4 gene expression level was also quantitated by real time-RT-PCR in CD34+ cells.
  
  
  RESULTS
  The expression of CXCR4 on circulating CD34+ cells was significantly reduced in patients with MMM (P<0.001) as compared to normal controls and patients with PV (P=0.01). The levels of CXCR4 mRNA in CD34+ cells were lower in patients with MMM as compared with normal subjects, and were directly correlated with the degree of CXCR4 surface expression, demonstrating that transcriptional defects were the major cause for receptor down-regulation. No statistical association was found between JAK2V617F mutational status and the extent of CXCR4 down-regulation. CXCR4 expression on CD34+ cells inversely correlated with the number of circulating CD34+ cells (R=-0.55; P<0.001), and was severely down-regulated in high risk patients and patients with a high "myelodepletion severity index". CXCR4 down-regulation was associated with advanced patient age, the presence of severe anemia, thrombocytopenia, and degree of bone marrow fibrosis.
  
  
  CONCLUSIONS
  Reduced expression of CXCR4 by CD34+ cells is a characteristic of MMM which is associated with the constitutive mobilization of CD34+ cells and occurs in patients with advanced forms of the disease.
authors.affiliation: Transplant Research Area, IRCCS Policlinico S. Matteo, Viale Golgi 19, 27100 Pavia, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Rosti
authors.forename: Margherita
authors.initials: M
authors.lastname: Massa
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Vannucchi
authors.forename: Gaetano
authors.initials: G
authors.lastname: Bergamaschi
authors.forename: Rita
authors.initials: R
authors.lastname: Campanelli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pecci
authors.forename: Gianluca
authors.initials: G
authors.lastname: Viarengo
authors.forename: Valentina
authors.initials: V
authors.lastname: Meli
authors.forename: Monia
authors.initials: M
authors.lastname: Marchetti
authors.forename: Paola
authors.initials: P
authors.lastname: Guglielmelli
authors.forename: Edward
authors.initials: E
authors.lastname: Bruno
authors.forename: Mingjiang
authors.initials: M
authors.lastname: Xu
authors.forename: Ronald
authors.initials: R
authors.lastname: Hoffman
authors.forename: Giovanni
authors.initials: G
authors.lastname: Barosi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34; D015415:Biomarkers; D001773:Blood Cells / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D055728:Primary Myelofibrosis / Q000097:blood* / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism*; D012720:Severity of Illness Index
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; D012333:RNA, Messenger; D019718:Receptors, CXCR4