Blood cells, molecules & diseases · 2007
The expression of CXCR4 is down-regulated on the CD34+ cells of patients with myelofibrosis with myeloid metaplasia.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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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, Italian Registry of Myelofibrosis with Myeloid Metaplasia, Myeloproliferative Disorders Research Consortium
Аннотация
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.
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.