Skip to main content

Advertisement

SpringerLink
Log in

MicroRNA Expression Analysis in Patients with Primary Myelofibrosis, Polycythemia vera and Essential Thrombocythemia

  • Original Article
  • Published:
Indian Journal of Hematology and Blood Transfusion Aims and scope Submit manuscript

Abstract

MicroRNAs (miRNA) are small non-coding RNA molecules that play critical roles in cell differentiation, proliferation and apoptosis and thus regulate haematopoietic stem cells and committed progenitor cells. We analyzed expressions of miRNAs associated with hematopoietic transformation of myeloid, erythroid and megakaryocytic progenitor cells during haematopoiesis (mir155, mir181a, mir221, mir222, mir223, mir451), in patients with primary myelofibrosis (PMF) (n = 22), polycythemia vera (PV) (n = 33), essential thrombocythemia (ET) (n = 49) and in healthy controls (n = 40) by quantitate/real time polymerase chain reaction. RT-PCR testing was negative for BCR–ABL1 fusion gene in all the patients. Mir155 was expressed in higher levels in all 3 disorders (p < 0.05). Mir221 was higher especially in ET and PMF group (p < 0.05). Mir222 expression was lower in PV patients (p < 0.05) and higher in ET and PMF patients compared to control group. Mir223 expression was higher in ET and PMF group than control group (p > 0.05). Mir451 levels were lower in all three groups compared to control group (p < 0.05). There was no difference in expression levels of mir181a between groups. JAK2V617F positivity, co-morbidities, drugs, and gender did not affect miRNA expressions. This study holds promise for the future application of these molecules for differential diagnosis and as therapeutic targets in Philadelphia chromosome negative myeloproliferative neoplasms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Ambros V (2008) The evolution of our thinking about microRNAs. Nat Med 14:1036–1040

    Article  CAS  PubMed  Google Scholar 

  2. Ambros V (2004) The functions of animal microRNAs. Nature 431:350–355

    Article  CAS  PubMed  Google Scholar 

  3. O’Connell RM, Baltimore D (2012) MicroRNAs and hematopoietic cell development. Curr Top Dev Biol 99:145–174

    Article  PubMed  Google Scholar 

  4. Lawrie CH (2007) MicroRNAs and haematology: small molecules, big function. Br J Haematol 137:503–512

    Article  CAS  PubMed  Google Scholar 

  5. Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keatin M, Rai K, Rassenti L, Kipps T, Negrini M, Bullrich F, Croce CM (2002) Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 99:15524–15529

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Esquela-Kerscher A, Slack FJ (2006) Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer 6:259–269

    Article  CAS  PubMed  Google Scholar 

  7. Lujambio A, Calin GA, Villanueva A, Ropero S, Sánchez-Céspedes M, Blanco D, Montuenga LM, Rossi S, Nicoloso MS, Faller WJ, Gallagher WM, Eccles SA, Croce CM, Esteller M (2008) A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci USA 105:13556–13561

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Vannucchi AM, Guglielmelli P, Tefferi A (2009) Advances in understanding and management of myeloproliferative neoplasms. CA Cancer J Clin 59:171–191

    Article  PubMed  Google Scholar 

  9. Jones AV, Kreil S, Zoi K, Waghorn K, Curtis C, Zhang L, Score J, Seear R, Chase AJ, Grand FH, White H, Zoi C, Loukopoulos D, Terpos E, Vervessou EC, Schultheis B, Emig M, Ernst T, Lengfelder E, Hehlmann R, Hochhaus A, Oscier D, Silver RT, Reiter A, Cross NC (2005) Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders. Blood 106:2162–2168

    Article  CAS  PubMed  Google Scholar 

  10. Chen E, Beer PA, Godfrey AL, Ortmann CA, Li J, Costa-Pereira AP, Ingle CE, Dermitzakis ET, Campbell PJ, Green AR (2010) Distinct clinical phenotypes associated with JAK2V617F reflect differential STAT1 signaling. Cancer Cell 18:524–535

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Tefferi A, Vardiman JW (2008) Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia 22:14–22

    Article  CAS  PubMed  Google Scholar 

  12. Clement P, Valérie M, Gaëlle D, Emilie V, Patrick E, Nathalie LS (2010) Zip nucleic acids are potent hydrolysis probes for quantitative PCR. Nucl Acids Res 38:e95

    Article  Google Scholar 

  13. Fabbri M, Croce CM, Calin GA (2009) MicroRNAs in the ontogeny of leukemias and lymphomas. Leuk Lymphoma 50:160–170

    Article  CAS  PubMed  Google Scholar 

  14. Thai TH, Calado DP, Casola S, Ansel KM, Xiao C, Xue Y, Murphy A, Frendewey D, Valenzuela D, Kutok JL, Schmidt-Supprian M, Rajewsky N, Yancopoulos G, Rao A, Rajewsky K (2007) Regulation of the germinal center response by microRNA-155. Science 316:604–608

    Article  CAS  PubMed  Google Scholar 

  15. Georgantas RW, Hildreth R, Morisot S, Alder J, Liu CG, Heimfeld S, Calin GA, Croce CM, Civin CI (2007) CD34+hematopoietic stem-progenitor cell microRNA expression and function: a circuit diagram of differentiation control. Proc Natl Acad Sci USA 104:2750–2755

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Bruchova H, Yoon D, Agarwal AM, Mendell J, Prchal JT (2007) Regulated expression of microRNAs in normal and polycythemia vera erythropoiesis. Exp Hematol 35:1657–1667

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. O’Connell RM, Rao DS, Chaudhuri AA, Boldin MP, Taganov KD, Nicoll J, Paguette RL, Baltimore D (2008) Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder. J Exp Med 205:585–594

    Article  PubMed Central  PubMed  Google Scholar 

  18. Zhan H, Cardozo C, Raza A (2013) MicroRNAs in myeloproliferative neoplasms. Br J Haematol 161:471–483

    Article  CAS  PubMed  Google Scholar 

  19. Mendell JT, Olson EN (2012) MicroRNAs in stress signaling and human disease. Cell 148:1172–1187

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Tefferi A, Vaidya R, Caramazza D, Finke C, Lasho T, Pardanani A (2011) Circulating interleukin (IL)-8, IL-2R, IL-12, and IL-15 levels are independently prognostic in primary myelofibrosis: a comprehensive cytokine profiling study. J Clin Oncol 29:1356–1363

    Article  CAS  PubMed  Google Scholar 

  21. Chen C, Li L, Lodish HF, Bartel DP (2004) MicroRNAs modulate hematopoietic lineage differentiation. Science 303:83–86

    Article  CAS  PubMed  Google Scholar 

  22. Ebert PJ, Jiang S, Xie J, Li QJ, Davis MM (2009) An endogenous positively selecting peptide enhances mature T cell responses and becomes an autoantigen in the absence of microRNA miR-181a. Nat Immunol 10:1162–1169

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Bortoluzzi S, Bisognin A, Biasiolo M, Guglielmelli P, Biamonte F, Norfo R, Manfredini R, Vannucchi AM (2012) Characterization and discovery of novel miRNAs and moRNAs in JAK2V617F-mutated SET2 cells. Blood 119:120–130

    Article  Google Scholar 

  24. Felli N, Fontana L, Pelosi E, Botta R, Bonci D, Facchiano F, Liuzzi F, Lulli V, Morsilli O, Santoro S, Valtieri M, Calin GA, Liu CG, Sorrentino A, Croce CM, Peschle C (2005) MicroRNAs 221 and 222 inhibit normal erythropoiesis and erythroleukemic cell growth via kit receptor down-modulation. Proc Natl Acad Sci USA 102:18081–18086

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Felli N, Pedini F, Romania P, Biffoni M, Morsilli O, Castelli G, Santoro S, Chicarella S, Sorrentino A, Peschle C, Marziali G (2009) MicroRNA 223-dependent expression of LMO2 regulates normal erythropoiesis. Haematologica 94:479–486

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Fazi F, Rosa A, Fatica A, Gelmetti V, De Marchis ML, Nervi C, Bozzoni I (2005) A minicircuitry comprised of micro-RNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis. Cell 123:819–831

    Article  CAS  PubMed  Google Scholar 

  27. Bruchova H, Merkerova M, Prchal JT (2008) Aberrant expression of microRNA in polycythemia vera. Haematologica 93:1009–1016

    Article  CAS  PubMed  Google Scholar 

  28. Zhan H, Cardozo C, Yu W, Wang A, Moliterno AR, Dang CV, Spivak JL (2013) MicroRNA deregulation in polycythemia vera and essential thrombocythemia patients. Blood Cells Mol Dis 50:190–195

    Article  CAS  PubMed  Google Scholar 

  29. Bruchova-Votavova H, Yoon D, Prchal JT (2010) MiR-451 enhances erythroid differentiation in K562 cells. Leuk Lymphoma 51:686–693

    Article  CAS  PubMed  Google Scholar 

  30. Rasmussen KD, Simmini S, Abreu-Goodger C, Bartonicek N, Di Giacomo M, Bilbao-Cortes D, Horos R, Von Lindern M, Enright AJ, O’Carroll D (2010) The miR-144/451 locus is required for erythroid homeostasis. J Exp Med 207:1351–1358

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Girardot M, Pecquet C, Boukour S, Knoops L, Ferrant A, Vainchenker W, Giraudier S, Constantinescu SN (2010) MiR-28 is a thrombopoietin receptor targeting microRNA detected in a fraction of myeloproliferative neoplasm patient platelets. Blood 116:437–445

    Article  CAS  PubMed  Google Scholar 

  32. Wang L, Zhang H, Rodriguez S, Cao L, Parish J, Mumaw C, Zollman A, Kamoka MM, Mu J, Chen DZ, Srour EF, Chitteti BR, HogenEsch H, Tu X, Bellido TM, Boswell HS, Manshouri T, Verstovsek S, Yoder MC, Kapur R, Cardoso AA, Carlesso N (2014) Notch-dependent repression of miR-155 in the bone marrow niche regulates hematopoiesis in an NF-κB-dependent manner. Cell Stem Cell 3:51–65

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Hematology, Mersin University Faculty of Medicine, Mersin, Turkey

    Anil Tombak, Mehmet Ali Ucar, Aydan Akdeniz & Eyup Naci Tiftik

  2. Department of Genetics, Mersin University Faculty of Medicine, Mersin, Turkey

    Ozlem Izci Ay & Mehmet Emin Erdal

  3. Department of Biostatistics, Mersin University Faculty of Medicine, Mersin, Turkey

    Mehmet Ali Sungur

Authors
  1. Anil Tombak
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ozlem Izci Ay
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mehmet Emin Erdal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mehmet Ali Sungur
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mehmet Ali Ucar
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Aydan Akdeniz
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Eyup Naci Tiftik
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anil Tombak.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tombak, A., Ay, O.I., Erdal, M.E. et al. MicroRNA Expression Analysis in Patients with Primary Myelofibrosis, Polycythemia vera and Essential Thrombocythemia. Indian J Hematol Blood Transfus 31, 416–425 (2015). https://doi.org/10.1007/s12288-014-0492-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12288-014-0492-z

Keywords

Search

Navigation