Abstract
Immune thrombocytopenia (ITP) is a common autoimmune disorder characterized by decreased platelet count (thrombocytopenia) and bleeding symptoms due to production of autoantibodies against platelets. Chemokines are molecules inducing chemotaxis and play an important role in megakaryopoiesis, including CXCR4 chemokine receptor. CXCR4 is expressed on cells of megakaryocytic series, especially platelets, and triggers several mechanisms in these cells. The purpose of this study was to evaluate the pattern of CXCR4 gene changes upon diagnosis and after treatment and its comparison with laboratory findings in peripheral blood samples from newly diagnosed ITP patients. 35 newly diagnosed patients with ITP and 35 healthy controls were enrolled in this study. CXCR4 gene expression was investigated before and after treatment using real-time PCR. HPRT gene was used as the reference gene to calculate the expression rate of CXCR4 as CXCR4/HPRT ratio. CXCR4 gene expression upon diagnosis and after treatment in peripheral blood plasma of ITP patients showed a significant decrease in comparison with the control group while its expression did not change before and after treatment. No significant correlation was found between the expression of this gene and laboratory parameters. Due to unpredictable course of ITP in patients and the possibility of its progress to refractory form, accurate choice of a biomarker is essential for evaluating prognosis and detection of resistant forms.
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References
Stasi R, Newland AC (2011) ITP: a historical perspective. Br J Haematol 153(4):437–450
Saeidi S, Jaseb K, Asnafi AA, Rahim F, Pourmotahari F, Mardaniyan S et al (2014) Immune thrombocytopenic purpura in children and adults: a comparative retrospective study in Iran. Int J Hematol Oncol Stem Cell Res 8(3):30–36
Gu D, Chen Z, Zhao H, Du W, Xue F, Ge J et al (2010) Th1 (CXCL10) and Th2 (CCL2) chemokine expression in patients with immune thrombocytopenia. Hum Immunol 71(6):586–591
Ku FC, Tsai CR, Wang J, Wang CH, Chang TK, Hwang WL (2013) Stromal-derived factor-1 gene variations in pediatric patients with primary immune thrombocytopenia. Eur J Haematol 90(1):25–30
Wang JF, Liu ZY, Groopman JE (1998) The alpha-chemokine receptor CXCR4 is expressed on the megakaryocytic lineage from progenitor to platelets and modulates migration and adhesion. Blood 92(3):756–764
Bustin SA, Benes V, Garson JA, Hellemans J, Huggett J, Kubista M et al (2009) The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin Chem 55(4):611–622
George JN, Woolf SH, Raskob GE, Wasser J, Aledort L, Ballem P et al (1996) Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood 88(1):3–40
Anoop P (2012) Immune thrombocytopenic purpura: historical perspective, current status, recent advances and future directions. Indian Pediatr 49(10):811–818
Johnsen J (2012) Pathogenesis in immune thrombocytopenia: new insights. ASH Educ Program Book 2012(1):306–312
Zhou B, Zhao H, Yang RC, Han ZC (2005) Multi-dysfunctional pathophysiology in ITP. Crit Rev Oncol Hematol 54(2):107–116
Wendling F, Han Z-C (1997) 2 Positive and negative regulation of megakaryocytopoiesis. Baillières Clin Haematol 10(1):29–45
Machlus KR, Thon JN, Italiano JE (2014) Interpreting the developmental dance of the megakaryocyte: a review of the cellular and molecular processes mediating platelet formation. Br J Haematol 165(2):227–236
Deutsch VR, Tomer A (2006) Megakaryocyte development and platelet production. Br J Haematol 134(5):453–466
Abi-Younes S, Sauty A, Mach F, Sukhova G, Libby P, Luster A (2000) The stromal cell–derived factor-1 chemokine is a potent platelet agonist highly expressed in atherosclerotic plaques. Circ Res 86(2):131–138
Deutsch V, Bitan M, Friedmann Y, Eldor A, Vlodavsky I (2000) Megakaryocyte maturation is associated with expression of the CXC chemokine connective tissue-activating peptide CTAP III. Br J Haematol 111(4):1180–1189
Gear AR, Camerini D (2003) Platelet chemokines and chemokine receptors: linking hemostasis, inflammation, and host defense. Microcirculation 10(3–4):335–350
Hodohara K, Fujii N, Yamamoto N, Kaushansky K (2000) Stromal cell-derived factor-1 (SDF-1) acts together with thrombopoietin to enhance the development of megakaryocytic progenitor cells (CFU-MK). Blood 95(3):769–775
Rivière C, Subra F, Cohen-Solal K, Cordette-Lagarde V, Letestu R, Auclair C et al (1999) Phenotypic and functional evidence for the expression of CXCR4 receptor during megakaryocytopoiesis. Blood 93(5):1511–1523
Labbaye C, Spinello I, Quaranta MT, Pelosi E, Pasquini L, Petrucci E et al (2008) A three-step pathway comprising PLZF/miR-146a/CXCR4 controls megakaryopoiesis. Nat Cell Biol 10(7):788–801
Scaradavou A (2002) HIV-related thrombocytopenia. Blood Rev 16(1):73–76
Feng X, Scheinberg P, Samsel L, Rios O, Chen J, McCOY J et al (2012) Decreased plasma cytokines are associated with low platelet counts in aplastic anemia and immune thrombocytopenic purpura. J Thromb Haemost 10(8):1616–1623
Wang A, Guilpain P, Chong BF, Chouzenoux S, Guillevin L, Du Y et al (2010) Dysregulated expression of CXCR4/CXCL12 in subsets of patients with systemic lupus erythematosus. Arthritis Rheum 62(11):3436–3446
Ahn JY, Seo K, Weinberg OK, Arber DA (2013) The prognostic value of CXCR4 in acute myeloid leukemia. Appl Immunohistochem Mol Morphol 21(1):79–84
Salim JP, Goette NP, Lev PR, Chazarreta CD, Heller PG, Alvarez C et al (2009) Dysregulation of stromal derived factor 1/CXCR4 axis in the megakaryocytic lineage in essential thrombocythemia. Br J Haematol 144(1):69–77
Kowalska MA, Ratajczak J, Hoxie J, Brass LF, Gewirtz A, Poncz M et al (1999) Megakaryocyte precursors, megakaryocytes and platelets express the HIV co-receptor CXCR4 on their surface: determination of response to stromal-derived factor-1 by megakaryocytes and platelets. Br J Haematol 104(2):220–229
Wang J-D, Ou T-T, Wang C-J, Chang T-K, Lee H-J (2010) Platelet apoptosis resistance and increased CXCR4 expression in pediatric patients with chronic immune thrombocytopenic purpura. Thromb Res 126(4):311–318
Olsson B, Ridell B, Carlsson L, Jacobsson S, Wadenvik H (2008) Recruitment of T cells into bone marrow of ITP patients possibly due to elevated expression of VLA-4 and CX3CR1. Blood 112(4):1078–1084
Pitchford SC, Lodie T, Rankin SM (2012) VEGFR1 stimulates a CXCR4-dependent translocation of megakaryocytes to the vascular niche, enhancing platelet production in mice. Blood 120(14):2787–2795
Janz JM, Ren Y, Looby R, Kazmi MA, Sachdev P, Grunbeck A et al (2011) Direct interaction between an allosteric agonist pepducin and the chemokine receptor CXCR4. J Am Chem Soc 133(40):15878–15881
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This work was financially supported by grant TH93/4 from vice chancellor for research affairs of Ahvaz Jundishapur University of Medical Sciences. This paper is issued from thesis of Sajedeh Saeidi.
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Saeidi, S., Mohammadi-Asl, J., Far, M.A.J. et al. Is There a Relationship Between CXCR4 Gene Expression and Prognosis of Immune Thrombocytopenia in Children?. Indian J Hematol Blood Transfus 33, 216–221 (2017). https://doi.org/10.1007/s12288-016-0648-0
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DOI: https://doi.org/10.1007/s12288-016-0648-0