Reduced CXCR4-expression on CD34-positive blood cells predicts outcomes of persons with primary myelofibrosis

Giovanni Barosi, Vittorio Rosti, Paolo Catarsi, Laura Villani, Carlotta Abbà, Adriana Carolei, Umberto Magrini, Robert Peter Gale, Margherita Massa, Rita Campanelli

Research output: Contribution to journalArticle

Abstract

The expression of the CXCR4 chemokine receptor on CD34-positive blood cells is reduced in persons with primary myelofibrosis (PMF). We analyzed the relevance of cytofluorimetric assessment of the percentage of CD34-positive blood cells that had a positive CXCR4 surface expression (CD34/CXCR4-se) in a large cohort of subjects with myeloproliferative neoplasms. Mean CD34/CXCR4-se was lower in subjects with PMF compared with those with essential thrombocythemia (ET) or polycythemia vera (PV). A cutoff value of 39% was associated with a diagnosis of pre-fibrotic PMF vs. ET with a positive predictive value of 97%. In PMF male sex, older age, and MPL mutation were independent correlates of reduced CD34/CXCR4-se and associated with a briefer interval to development of severe anemia, large splenomegaly, thrombocytopenia, leukopenia, elevated CD34-positive blood cells, blast transformation and death. We constructed a prognostic model including age >65 years, hemoglobin < 100 g/L, CD34-positive blood cells > 50 × 106/L, and CD34/CXCR4-se <39% at diagnosis. The model identified three risk cohorts with greater accuracy compared with the International Prognostic Scoring System. In conclusion, CD34/CXCR4-se is a highly sensitive marker of disease activity and a new potential diagnostic and prognostic biomarker in PMF.

Original languageEnglish
JournalLeukemia
DOIs
Publication statusAccepted/In press - Jan 1 2020

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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