title: Proliferative characteristics of Philadelphia-negative myeloproliferative neoplasms - clinical implications.
abstract: BACKGROUND
  Philadelphia-negative myeloproliferative neoplasms (Ph-MPN) are characterized by overproduction of one or more blood cell lines.
  
  
  METHODS
  We studied the proliferative characteristics of 91 patients with de novo Ph-MPN. Colony-forming cells (CFC) and endogenous colonies (EC), from bone marrow (BM) and/or peripheral blood (PB), were analyzed by colony assay based on methylcellulose. The level of circulating CD34+cells was determined by flow cytometry.
  
  
  RESULTS
  The total number of PB CFC in primary myelofibrosis (PMF) was increased compared to the control sample (P < 0.01) and essential thrombocythemia (ET) (P < 0.05). The highest number of BM and PB EC was observed in polycythemia vera (PV) (P < 0.01). Increased levels of CD34+cells characterized early-prefibrotic (57%) and advanced-fibrotic PMF (90%) as compared to PV (34%) and ET (32%) (P < 0.01). In the whole Ph-MPN group, the total number of PB CFC (P < 0.01), PB EC (P < 0.05), and CD34+cells (P < 0.01) correlated with the degree of BM fibrosis. Higher levels of circulating CD34+cells in PMF correlated with the total number of PB EC (P < 0.05) and degree of BM fibrosis (P < 0.01).
  
  
  CONCLUSIONS
  Exploration of the PB proliferative characteristics of Ph-MPN on diagnosis may be helpful in revealing early-prefibrotic PMF. Monitoring the levels of circulating CD34+cells may provide a sensitive indicator of fibrotic evolution in PV and PMF.
authors.affiliation: Outpatient Clinic and Diagnostic Department, Clinic of Hematology, Clinical Center of Serbia, Belgrade, Serbia.
authors.forename: D
authors.initials: D
authors.lastname: Šefer
authors.affiliation: Outpatient Clinic and Diagnostic Department, Clinic of Hematology, Clinical Center of Serbia, Belgrade, Serbia.
authors.forename: S
authors.initials: S
authors.lastname: Bižić-Radulović
authors.affiliation: Outpatient Clinic and Diagnostic Department, Clinic of Hematology, Clinical Center of Serbia, Belgrade, Serbia.
authors.forename: N
authors.initials: N
authors.lastname: Kraguljac-Kurtović
authors.affiliation: Outpatient Clinic and Diagnostic Department, Clinic of Hematology, Clinical Center of Serbia, Belgrade, Serbia.|Medical Faculty University of Belgrade, Belgrade, Serbia.
authors.forename: A
authors.initials: A
authors.lastname: Bogdanović
authors.affiliation: Medical Faculty University of Belgrade, Belgrade, Serbia.|Laboratory of Experimental Hematology, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: V
authors.identifier: http://orcid.org/0000-0002-0362-1449
authors.initials: V
authors.lastname: Čokić
authors.affiliation: Outpatient Clinic and Diagnostic Department, Clinic of Hematology, Clinical Center of Serbia, Belgrade, Serbia.|Medical Faculty University of Belgrade, Belgrade, Serbia.
authors.forename: P
authors.initials: P
authors.lastname: Miljić
authors.affiliation: Clinic of Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia, Belgrade, Serbia.
authors.forename: B
authors.initials: B
authors.lastname: Beleslin-Čokić
authors.affiliation: Outpatient Clinic and Diagnostic Department, Clinic of Hematology, Clinical Center of Serbia, Belgrade, Serbia.
authors.forename: V
authors.initials: V
authors.lastname: Knežević
authors.affiliation: Medical Faculty University of Belgrade, Belgrade, Serbia.|Laboratory of Experimental Hematology, Institute for Medical Research, University of Belgrade, Belgrade, Serbia.
authors.forename: O
authors.initials: O
authors.lastname: Mitrović-Ajtić
authors.affiliation: Outpatient Clinic and Diagnostic Department, Clinic of Hematology, Clinical Center of Serbia, Belgrade, Serbia.|Medical Faculty University of Belgrade, Belgrade, Serbia.
authors.forename: D
authors.initials: D
authors.lastname: Leković
authors.affiliation: Outpatient Clinic and Diagnostic Department, Clinic of Hematology, Clinical Center of Serbia, Belgrade, Serbia.|Medical Faculty University of Belgrade, Belgrade, Serbia.
authors.forename: M
authors.initials: M
authors.lastname: Gotić
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D049109:Cell Proliferation; D005260:Female; D019337:Hematologic Neoplasms / Q000097:blood* / Q000175:diagnosis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000097:blood* / Q000175:diagnosis*; D010677:Philadelphia Chromosome; D014407:Tumor Cells, Cultured
keywords: CD34+ cells; JAK2V617F; Myeloproliferative neoplasm; colony-forming cells; endogenous colonies