Molecular Biology Reports

, Volume 36, Issue 6, pp 1555–1557

Absence of JAK2 V617F mutation in thalassemia intermedia patients

  • Ali Taher
  • Dina Shammaa
  • Ali Bazarbachi
  • Doha Itani
  • Ghazi Zaatari
  • Layal Greige
  • Zaher K. Otrock
  • Rami A. R. Mahfouz
Article

Abstract

JAK2 is a cytoplasmic tyrosine kinase that has a vital role in signal transduction from several hemopoietic growth factor receptors. The JAK2 V617F mutation has been implicated in a variety of diseases mainly related to myeloproliferative disorders including polycythemia Vera, essential thrombocythemia, and idiopathic Myelofibrosis but has not been previously described in Thalassemia patients. We studied 36 Lebanese patients diagnosed with thalassemia intermedia and assessed the presence or absence of the JAK2 V617F mutation using JAK2 activating mutation assay (In VivoScribe Technologies) and Polymerase Chain Reaction (PCR). None of the thalassemia intermedia patients were positive for this mutation. To our knowledge, this study is the first to determine the status of JAK2 V617F mutation in thalassemia intermedia patients and expands the international published literature on JAK2. The latter’s V617F mutation does not seem to play a role in this hematologically important clinical entity.

Keywords

Thalassemia Intermedia JAK2 V617F Mutation 

References

  1. 1.
    Komura E, Chagraoui H, Mansat de Mas V, Blanchet B, de Sepulveda P, Larbret F, Larghero J, Tulliez M, Debili N, Vainchenker W, Giraudier S (2003) Spontaneous STAT5 activation induces growth factor independence in idiopathic myelofibrosis: possible relationship with FKBP51 overexpression. Exp Hematol 31:622–630PubMedCrossRefGoogle Scholar
  2. 2.
    Ugo V, Marzac C, Teyssandier I, Larbret F, Lécluse Y, Debili N, Vainchenker W, Casadevall N (2004) Multiple signaling pathways are involved in erythropoietin-independent differentiation of erythroid progenitors in polycythemia Vera. Exp Hematol 32:179–187PubMedCrossRefGoogle Scholar
  3. 3.
    Saharinen P, Takaluoma K, Silvennoinen O (2000) Regulation of the JAK2 tyrosine kinase by its pseudokinase domain. Mol Cell Biol 20:3387–3395PubMedCrossRefGoogle Scholar
  4. 4.
    Zhao R, Xing S, Li Z, Fu X, Li Q, Krantz SB, Zhao ZJ (2005) Identification of an acquired JAK2 mutation in polycythemia Vera. J Biol Chem 280:22788–22792PubMedCrossRefGoogle Scholar
  5. 5.
    Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR, Tichelli A, Cazzola M, Skoda RC (2005) A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 352:1779–1790PubMedCrossRefGoogle Scholar
  6. 6.
    Witthuhn BA, Quelle FW, Silvennoinen O, Yi T, Tang B, Miura O, Ihle JN (1993) JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin. Cell 74:227–236PubMedCrossRefGoogle Scholar
  7. 7.
    Socolovsky M, Fallon AE, Wang S, Brugnara C, Lodish HF (1999) Fetal anemia and apoptosis of red cell progenitors in STAT5A-/-5B-/- mice: a direct role for STAT5 in Bcl-X(L) induction. Cell 98:181–191PubMedCrossRefGoogle Scholar
  8. 8.
    Myklebust JH, Blomhoff HK, Rusten LS, Stokke T, Smeland EB (2002) Activation of phosphatidylinositol 3-kinase is important for erythropoietin-induced erythropoiesis from CD34 (+) hematopoietic progenitor cells. Exp Hematol 30:990–1000PubMedCrossRefGoogle Scholar
  9. 9.
    Krantz SB (1991) Erythropoietin. Blood 77:419–434PubMedGoogle Scholar
  10. 10.
    D’Andrea AD, Lodish HF, Wong GG (1989) Expression cloning of the murine erythropoietin receptor. Cell 57:277–285PubMedCrossRefGoogle Scholar
  11. 11.
    Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S, Vassiliou GS, Bench AJ, Boyd EM, Curtin N, Scott MA, Erber WN, Green AR, Cancer Genome Project (2005) Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 365:1054–1061PubMedGoogle Scholar
  12. 12.
    Levine RL, Belisle C, Wadleigh M, Zahrieh D, Lee S, Chagnon P, Gilliland DG, Busque L (2006) X-inactivation-based clonality analysis and quantitative JAK2 V617F assessment reveal a strong association between clonality and JAK2 V617F in PV but not ET/MMM, and identifies a subset of JAK2 V617F-negative ET and MMM patients with clonal hematopoiesis. Blood 107:4139–4141PubMedCrossRefGoogle Scholar
  13. 13.
    Campbell PJ, Griesshammer M, Döhner K, Döhner H, Kusec R, Hasselbalch HC, Larsen TS, Pallisgaard N, Giraudier S, Le Bousse-Kerdilès MC, Desterke C, Guerton B, Dupriez B, Bordessoule D, Fenaux P, Kiladjian JJ, Viallard JF, Brière J, Harrison CN, Green AR, Reilly JT (2006) V617F mutation in JAK2 is associated with poorer survival in idiopathic myelofibrosis. Blood 107:2098–2100PubMedCrossRefGoogle Scholar
  14. 14.
    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 106:2162–2168PubMedCrossRefGoogle Scholar
  15. 15.
    Steensma DP, Dewald GW, Lasho TL, Powell HL, McClure RF, Levine RL, Gilliland DG, Tefferi A (2005) The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both “atypical” myeloproliferative disorders and myelodysplastic syndromes. Blood 106:1207–1209PubMedCrossRefGoogle Scholar
  16. 16.
    Scott LM, Campbell PJ, Baxter EJ, Todd T, Stephens P, Edkins S, Wooster R, Stratton MR, Futreal PA, Green AR (2005) The V617F JAK2 mutation is uncommon in cancers and in myeloid malignancies other than the classic myeloproliferative disorders. Blood 106:2920–2921PubMedCrossRefGoogle Scholar
  17. 17.
    Levine RL, Loriaux M, Huntly BJ, Loh ML, Beran M, Stoffregen E, Berger R, Clark JJ, Willis SG, Nguyen KT, Flores NJ, Estey E, Gattermann N, Armstrong S, Look AT, Griffin JD, Bernard OA, Heinrich MC, Gilliland DG, Druker B, Deininger MW (2005) The JAK2 V617F activating mutation occurs in chronic myelomonocytic leukemia and acute myeloid leukemia, but not in acute lymphoblastic leukemia or chronic lymphocytic leukemia. Blood 106:3377–3379PubMedCrossRefGoogle Scholar
  18. 18.
    Jelinek J, Oki Y, Gharibyan V, Bueso-Ramos C, Prchal JT, Verstovsek S, Beran M, Estey E, Kantarjian HM, Issa JP (2005) JAK2 mutation 1849G>T is rare in acute leukemia’s but can be found in CMML, Philadelphia chromosome-negative CML, and megakaryocytic leukemia. Blood 106:3370–3373PubMedCrossRefGoogle Scholar
  19. 19.
    Fröhling S, Lipka DB, Kayser S, Scholl C, Schlenk RF, Döhner H, Gilliland DG, Levine RL, Döhner K (2006) Rare occurrence of the JAK2 V617F mutation in AML subtypes M5, M6, and M7. Blood 107:1242–1243PubMedCrossRefGoogle Scholar
  20. 20.
    Aessopos A, Kati M, Meletis J (2007) Thalassemia intermedia today: should patients regularly receive transfusions? Transfusion 47:792–800PubMedCrossRefGoogle Scholar
  21. 21.
    Olivieri NF (1999) The beta-thalassemias. N Engl J Med 341:99–109PubMedCrossRefGoogle Scholar
  22. 22.
    Camaschella C, Cappellini MD (1995) Thalassemia intermedia. Haematologica 80:58–68PubMedGoogle Scholar
  23. 23.
    Campbell PJ, Scott LM, Buck G, Wheatley K, East CL, Marsden JT, Duffy A, Boyd EM, Bench AJ, Scott MA, Vassiliou GS, Milligan DW, Smith SR, Erber WN, Bareford D, Wilkins BS, Reilly JT, Harrison CN, Green AR, United Kingdom Myeloproliferative Disorders Study Group, Medical Research Council Adult Leukaemia Working Party, Australasian Leukaemia and Lymphoma Group (2005) Definition of subtypes of essential thrombocythemia and relation to polycythemia Vera based on JAK2 V617F mutation status: a prospective study. Lancet 366:1945–1953PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Ali Taher
    • 1
  • Dina Shammaa
    • 2
  • Ali Bazarbachi
    • 1
  • Doha Itani
    • 2
  • Ghazi Zaatari
    • 2
  • Layal Greige
    • 2
  • Zaher K. Otrock
    • 2
  • Rami A. R. Mahfouz
    • 2
  1. 1.Department of Internal MedicineAmerican University of Beirut Medical Center (AUBMC)BeirutLebanon
  2. 2.Department of Pathology & Laboratory MedicineAmerican University of Beirut Medical Center (AUBMC)BeirutLebanon

Personalised recommendations