title: Proteolytic matrix metallopeptidases and inhibitors in BCR-ABL1-negative myeloproliferative neoplasms: correlation with JAK2 mutation status.
abstract: OBJECTIVE
  Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) share the same acquired lesion JAK2(V617F) and may exhibit substantial overlap. Variability in JAK activation and allele burden, complemented by host, genetic and non-genetic modifiers, determine the phenotype. The aim of this study was to investigate the presence of the JAK2 mutation in association with the ratio of metallopeptidases inhibitors (TIMPs) to tissue metallopeptidases (MMPs) in MPNs, where inhibitory rather than proteolytic activity in marrow microenvironment appears to predominate.
  
  
  METHODS
  94 patients with polycythemia vera, essential thrombocythemia and primary myelofibrosis, and 102 healthy individuals were evaluated. Allele-specific PCR and RFLP were used to detect JAK2 and genomic status. Serum concentrations of MMP and TIMP were measured by ELISA. The parameters were assessed with covariance analysis, and adjusted for gender, age and co-morbidity.
  
  
  RESULTS
  Mutation frequency was 81.91%. Abnormal TIMP/MMP ratios were identified in all three diseases. JAK2 mutation was correlated with significant changes in TIMP concentrations.
  
  
  CONCLUSIONS
  Identification of an abnormal TIMP/MMP ratio in all three diseases, regardless of the JAK2 status, indicates invariable marrow remodeling. In this particular group of patients, presence of a JAK2(V617F) mutation, being associated with even higher ratios, appears to be a concurring participant in bone marrow-reforming processes. Additional research may delineate correlates with the JAK2 allelic burden.
authors.affiliation: Department of Hematology, Democritus University Medical School, Alexandroupolis, Greece.
authors.forename: C M
authors.initials: CM
authors.lastname: Vadikolia
authors.forename: C
authors.initials: C
authors.lastname: Tsatalas
authors.forename: K
authors.initials: K
authors.lastname: Anagnostopoulos
authors.forename: G
authors.initials: G
authors.lastname: Trypsianis
authors.forename: D
authors.initials: D
authors.lastname: Pantelidou
authors.forename: I
authors.initials: I
authors.lastname: Bazdiara
authors.forename: A
authors.initials: A
authors.lastname: Anastasiadis
authors.forename: E
authors.initials: E
authors.lastname: Spanoudakis
authors.forename: I
authors.initials: I
authors.lastname: Kotsianidis
authors.forename: D
authors.initials: D
authors.lastname: Margaritis
authors.forename: A
authors.initials: A
authors.lastname: Kortsaris
authors.forename: G
authors.initials: G
authors.lastname: Bourikas
mesh_terms: D000368:Aged; D005260:Female; D016313:Genes, abl; D006801:Humans; D006868:Hydrolysis; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology*
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D020782:Matrix Metalloproteinases