Epigenetic alteration of SOCS family members is a possible pathogenetic mechanism in JAK2 wild type myeloproliferative diseases

Luciana Teofili, Maurizio Martini, Tonia Cenci, Francesco Guidi, Lorenza Torti, Fiorina Giona, Robin Foà, Giuseppe Leone, Luigi Maria Larocca

Risultato della ricerca: Contributo in rivistaArticolo in rivista

40 Citazioni (Scopus)


In polycythemia vera (PV) and essential thrombocythemia (ET) specific JAK2 mutations constitutively activate the JAK-STAT pathway, explaining biologic findings such as endogenous erythroid colony (EECs) growth or PRV-1 RNA overexpression. Since these markers are detected also in JAK2 wild type patients, we hypothesized that, in these cases, the activation of the JAK-STAT pathway could be produced by a deregulation of the suppressor of cytokine signaling (SOCS) protein system. Eighty-one patients with PV and ET (53 adults and 28 children) were investigated for the methylation status of the SOCS-1, SOCS-2 and SOCS-3 CpG islands and for several myeloproliferative markers (including JAK2 and MPL mutations and clonality of hematopoiesis). SOCS-1 or SOCS-3 hypermethylation was identified in 23 patients and was associated with a significant decrease of SOCS-1 or SOCS-3 RNA and protein levels. The gene expression was restored by exposing cells to the demethylating agent 2-deoxyazacytidin. Interestingly, SOCS-1 or SOCS-3 hypermethylation was detected in 6 female patients, proved negative for JAK2 or MPL mutations and exhibiting monoclonal hematopoiesis. In conclusion, SOCS-1 or SOCS-3 hypermethylation can activate the JAK-STAT signaling pathway in alternative or together with JAK2 mutations. These alterations might represent a potential therapeutic target.
Lingua originaleEnglish
pagine (da-a)1586-1592
Numero di pagine7
RivistaInternational Journal of Cancer
Stato di pubblicazionePubblicato - 2008


  • Adolescent
  • Aged
  • Aged, 80 and over
  • Base Sequence
  • Blotting, Western
  • CpG Islands
  • DNA Methylation
  • DNA Primers
  • Epigenesis, Genetic
  • Female
  • Humans
  • Immunohistochemistry
  • Janus Kinase 2
  • Male
  • Middle Aged
  • Mutation
  • Polycythemia Vera
  • Reverse Transcriptase Polymerase Chain Reaction
  • Suppressor of Cytokine Signaling Proteins
  • Thrombocythemia, Essential


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