The expression of CXCR4 is down-regulated on the CD34+ cells of patients with myelofibrosis with myeloid metaplasia

Vittorio Rosti, Margherita Massa, Alessandro M. Vannucchi, Gaetano Bergamaschi, Rita Campanelli, Alessandro Pecci, Gianluca Viarengo, Valentina Meli, Monia Marchetti, Paola Guglielmelli, Edward Bruno, Mingjiang Xu, Ronald Hoffman, Giovanni Barosi

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Abstract

Purpose: We studied the expression of the chemokine receptor CXCR4 on circulating CD34+ cells of patients with myelofibrosis with myeloid metaplasia (MMM), and examined its relationship to the severity of disease. Patients and methods: Surface and intracellular CXCR4 expression were measured flow cytometrically in 84 consecutive MMM patients, 16 patients with polycythemia vera (PV), and 20 healthy subjects. In 23 MMM patients, CXCR4 gene expression level was also quantitated by real time-RT-PCR in CD34+ cells. Results: The expression of CXCR4 on circulating CD34+ cells was significantly reduced in patients with MMM (P <0.001) as compared to normal controls and patients with PV (P = 0.01). The levels of CXCR4 mRNA in CD34+ cells were lower in patients with MMM as compared with normal subjects, and were directly correlated with the degree of CXCR4 surface expression, demonstrating that transcriptional defects were the major cause for receptor down-regulation. No statistical association was found between JAK2V617F mutational status and the extent of CXCR4 down-regulation. CXCR4 expression on CD34+ cells inversely correlated with the number of circulating CD34+ cells (R = - 0.55; P <0.001), and was severely down-regulated in high risk patients and patients with a high "myelodepletion severity index". CXCR4 down-regulation was associated with advanced patient age, the presence of severe anemia, thrombocytopenia, and degree of bone marrow fibrosis. Conclusions: Reduced expression of CXCR4 by CD34+ cells is a characteristic of MMM which is associated with the constitutive mobilization of CD34+ cells and occurs in patients with advanced forms of the disease.

Original languageEnglish (US)
Pages (from-to)280-286
Number of pages7
JournalBlood Cells, Molecules and Diseases
Volume38
Issue number3
DOIs
StatePublished - May 2007
Externally publishedYes

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Primary Myelofibrosis
Polycythemia Vera
Down-Regulation
Chemokine Receptors
Thrombocytopenia
Anemia
Real-Time Polymerase Chain Reaction
Healthy Volunteers

Keywords

  • CXCR4
  • Mobilization
  • Myelofibrosis
  • SDF-1

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Hematology

Cite this

The expression of CXCR4 is down-regulated on the CD34+ cells of patients with myelofibrosis with myeloid metaplasia. / Rosti, Vittorio; Massa, Margherita; Vannucchi, Alessandro M.; Bergamaschi, Gaetano; Campanelli, Rita; Pecci, Alessandro; Viarengo, Gianluca; Meli, Valentina; Marchetti, Monia; Guglielmelli, Paola; Bruno, Edward; Xu, Mingjiang; Hoffman, Ronald; Barosi, Giovanni.

In: Blood Cells, Molecules and Diseases, Vol. 38, No. 3, 05.2007, p. 280-286.

Research output: Contribution to journalArticle

Rosti, V, Massa, M, Vannucchi, AM, Bergamaschi, G, Campanelli, R, Pecci, A, Viarengo, G, Meli, V, Marchetti, M, Guglielmelli, P, Bruno, E, Xu, M, Hoffman, R & Barosi, G 2007, 'The expression of CXCR4 is down-regulated on the CD34+ cells of patients with myelofibrosis with myeloid metaplasia', Blood Cells, Molecules and Diseases, vol. 38, no. 3, pp. 280-286. https://doi.org/10.1016/j.bcmd.2007.01.003
Rosti, Vittorio ; Massa, Margherita ; Vannucchi, Alessandro M. ; Bergamaschi, Gaetano ; Campanelli, Rita ; Pecci, Alessandro ; Viarengo, Gianluca ; Meli, Valentina ; Marchetti, Monia ; Guglielmelli, Paola ; Bruno, Edward ; Xu, Mingjiang ; Hoffman, Ronald ; Barosi, Giovanni. / The expression of CXCR4 is down-regulated on the CD34+ cells of patients with myelofibrosis with myeloid metaplasia. In: Blood Cells, Molecules and Diseases. 2007 ; Vol. 38, No. 3. pp. 280-286.
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abstract = "Purpose: We studied the expression of the chemokine receptor CXCR4 on circulating CD34+ cells of patients with myelofibrosis with myeloid metaplasia (MMM), and examined its relationship to the severity of disease. Patients and methods: Surface and intracellular CXCR4 expression were measured flow cytometrically in 84 consecutive MMM patients, 16 patients with polycythemia vera (PV), and 20 healthy subjects. In 23 MMM patients, CXCR4 gene expression level was also quantitated by real time-RT-PCR in CD34+ cells. Results: The expression of CXCR4 on circulating CD34+ cells was significantly reduced in patients with MMM (P <0.001) as compared to normal controls and patients with PV (P = 0.01). The levels of CXCR4 mRNA in CD34+ cells were lower in patients with MMM as compared with normal subjects, and were directly correlated with the degree of CXCR4 surface expression, demonstrating that transcriptional defects were the major cause for receptor down-regulation. No statistical association was found between JAK2V617F mutational status and the extent of CXCR4 down-regulation. CXCR4 expression on CD34+ cells inversely correlated with the number of circulating CD34+ cells (R = - 0.55; P <0.001), and was severely down-regulated in high risk patients and patients with a high {"}myelodepletion severity index{"}. CXCR4 down-regulation was associated with advanced patient age, the presence of severe anemia, thrombocytopenia, and degree of bone marrow fibrosis. Conclusions: Reduced expression of CXCR4 by CD34+ cells is a characteristic of MMM which is associated with the constitutive mobilization of CD34+ cells and occurs in patients with advanced forms of the disease.",
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T1 - The expression of CXCR4 is down-regulated on the CD34+ cells of patients with myelofibrosis with myeloid metaplasia

AU - Rosti, Vittorio

AU - Massa, Margherita

AU - Vannucchi, Alessandro M.

AU - Bergamaschi, Gaetano

AU - Campanelli, Rita

AU - Pecci, Alessandro

AU - Viarengo, Gianluca

AU - Meli, Valentina

AU - Marchetti, Monia

AU - Guglielmelli, Paola

AU - Bruno, Edward

AU - Xu, Mingjiang

AU - Hoffman, Ronald

AU - Barosi, Giovanni

PY - 2007/5

Y1 - 2007/5

N2 - Purpose: We studied the expression of the chemokine receptor CXCR4 on circulating CD34+ cells of patients with myelofibrosis with myeloid metaplasia (MMM), and examined its relationship to the severity of disease. Patients and methods: Surface and intracellular CXCR4 expression were measured flow cytometrically in 84 consecutive MMM patients, 16 patients with polycythemia vera (PV), and 20 healthy subjects. In 23 MMM patients, CXCR4 gene expression level was also quantitated by real time-RT-PCR in CD34+ cells. Results: The expression of CXCR4 on circulating CD34+ cells was significantly reduced in patients with MMM (P <0.001) as compared to normal controls and patients with PV (P = 0.01). The levels of CXCR4 mRNA in CD34+ cells were lower in patients with MMM as compared with normal subjects, and were directly correlated with the degree of CXCR4 surface expression, demonstrating that transcriptional defects were the major cause for receptor down-regulation. No statistical association was found between JAK2V617F mutational status and the extent of CXCR4 down-regulation. CXCR4 expression on CD34+ cells inversely correlated with the number of circulating CD34+ cells (R = - 0.55; P <0.001), and was severely down-regulated in high risk patients and patients with a high "myelodepletion severity index". CXCR4 down-regulation was associated with advanced patient age, the presence of severe anemia, thrombocytopenia, and degree of bone marrow fibrosis. Conclusions: Reduced expression of CXCR4 by CD34+ cells is a characteristic of MMM which is associated with the constitutive mobilization of CD34+ cells and occurs in patients with advanced forms of the disease.

AB - Purpose: We studied the expression of the chemokine receptor CXCR4 on circulating CD34+ cells of patients with myelofibrosis with myeloid metaplasia (MMM), and examined its relationship to the severity of disease. Patients and methods: Surface and intracellular CXCR4 expression were measured flow cytometrically in 84 consecutive MMM patients, 16 patients with polycythemia vera (PV), and 20 healthy subjects. In 23 MMM patients, CXCR4 gene expression level was also quantitated by real time-RT-PCR in CD34+ cells. Results: The expression of CXCR4 on circulating CD34+ cells was significantly reduced in patients with MMM (P <0.001) as compared to normal controls and patients with PV (P = 0.01). The levels of CXCR4 mRNA in CD34+ cells were lower in patients with MMM as compared with normal subjects, and were directly correlated with the degree of CXCR4 surface expression, demonstrating that transcriptional defects were the major cause for receptor down-regulation. No statistical association was found between JAK2V617F mutational status and the extent of CXCR4 down-regulation. CXCR4 expression on CD34+ cells inversely correlated with the number of circulating CD34+ cells (R = - 0.55; P <0.001), and was severely down-regulated in high risk patients and patients with a high "myelodepletion severity index". CXCR4 down-regulation was associated with advanced patient age, the presence of severe anemia, thrombocytopenia, and degree of bone marrow fibrosis. Conclusions: Reduced expression of CXCR4 by CD34+ cells is a characteristic of MMM which is associated with the constitutive mobilization of CD34+ cells and occurs in patients with advanced forms of the disease.

KW - CXCR4

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KW - Myelofibrosis

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