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Chronic myeloproliferative neoplasms

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

Leukemia volume 35, pages 468–475 (2021)Cite this article

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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.

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Fig. 1: Comparative expression of blood CD34/CXCR4-se (mean ± 1.96 standard error) in the subtypes of MPNs and normals.
Fig. 2: Comparative expression of CD34/CXCR-se (mean ± 1.96 standard error) of subjects with primary myelofibrosis stratified according to the driver mutations genotypes.
Fig. 3: Overall survival curves.

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Authors and Affiliations

  1. Center for the Study of Myelofibrosis, Laboratory of Biochemistry, Biotechnology and Advanced Diagnostics, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo Foundation, Pavia, Italy

    Giovanni Barosi, Vittorio Rosti, Paolo Catarsi, Laura Villani, Adriana Carolei, Umberto Magrini & Rita Campanelli

  2. Laboratory of Biochemistry, Biotechnology and Advanced Diagnostics, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo Foundation, Pavia, Italy

    Carlotta Abbà & Margherita Massa

  3. Centre for Haematology Research, Imperial College London, London, UK

    Robert Peter Gale

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  1. Giovanni Barosi
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  4. Laura Villani
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Contributions

GB, VR, RC, and MM designed the study, collected data from patients in Pavia, analyzed the results, and wrote the manuscript. LV and PC helped with the JAK2V617F, CALR and MPL mutation detection. CA and AC helped in analyzing the results. UM helped with the revision of bone marrow histology. RPG critically revised for important intellectual content, helped with manuscript writing and data interpretation.

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Correspondence to Giovanni Barosi.

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Barosi, G., Rosti, V., Catarsi, P. et al. Reduced CXCR4-expression on CD34-positive blood cells predicts outcomes of persons with primary myelofibrosis. Leukemia 35, 468–475 (2021). https://doi.org/10.1038/s41375-020-0926-6

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