Abstract
Objective
JAK2 V617F, MPL W515L and JAK2 exon 12 mutations are novel acquired mutations that induce constitutive cytokine-independent activation of the JAK-STAT pathway in myeloproliferative disorders (MPD). The discovery of these mutations provides novel mechanism for activation of signal transduction in hematopoietic malignancies. This research was to investigate their prevalence in Chinese patients with primary myelofibrosis (PMF).
Methods
We introduced allele-specific PCR (AS-PCR) combined with sequence analysis to simultaneously screen JAK2 V617F, MPL W515L and JAK2 exon 12 mutations in 30 patients with PMF.
Results
Fifteen PMF patients (50.0%) carried JAK2 V617F mutation, and only two JAK2 V617F-negative patients (6.7%) harbored MPL W515L mutation. None had JAK2 exon 12 mutations. Furthermore, these three mutations were not detected in 50 healthy controls.
Conclusion
MPL W515L and JAK2 V617F mutations existed in PMF patients but JAK2 exon 12 mutations not. JAK2 V617F and MPL W515L and mutations might contribute to the primary molecular pathogenesis in patients with PMF.
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References
Dameshek W. Some speculations on the myeloproliferative syndromes. Blood 1951; 6:372–375.
Levine RL, Wadleigh M, Cools J, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis[J]. Cancer Cell 2005; 7:387–397.
Jones AV, Kreil S, Zoi K, et al. Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders. Blood 2005; 106:2162–2168.
James C, Ugo V, Le Couédic JP, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 2005; 434:1144–1148.
Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 2005; 365:1054–1061.
Kralovics R, Passamonti F, Buser AS, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 2005; 352:1779–1790.
Levine RL, Belisle C, Wadleigh M, et al: X-inactivation-based clonality analysis and quantitative JAK2V617F assessment reveal a strong association between clonality and JAK2V617F in PV but not ET/MMM, and identifies a subset of JAK2V617F-negative ET and MMM patients with clonal hematopoiesis. Blood 2006; 107:4139–4141.
Lippert E, Boissinot M, Kralovics R, et al. The JAK2-V617F mutation is frequently present at diagnosis in patients with essential thrombocythemia and polycythemia vera. Blood 2006; 108:1865–1867.
Nelson ME, Steensma DP. JAK2 V617F in myeloid disorders: what do we know now, and where are we headed? Leuk Lymphoma 2006; 47:177–194.
McClure R, Mai M, Lasho T. Validation of two clinically useful assays for evaluation of JAK2 V617F mutation in chronic myeloproliferative disorders. Leukemia 2006; 20:168–171.
Steensma DP, Dewald GW, Lasho TL, et al. The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both “atypical” myeloproliferative disorders and myelodysplastic syndromes. Blood 2005; 106:1207–1209.
Levine RL, Loriaux M, Huntly BJ, et al. The JAK2V617F activating mutation occurs in chronic myelomonocytic leukemia and acute myeloid leukemia, but not in acute lymphoblastic leukemia or chronic lymphocytic leukemia. Blood 2005; 106:3377–3379.
Beer PA, Campbell PJ, Scott LM, et al. MPL mutations in myeloproliferative disorders: analysis of the PT-1 cohort. Blood 2008; 112:141–149.
Pikman Y, Lee BH, Mercher T, et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med 2006; 3:e270.
Pardanani AD, Levine RL, Lasho T, et al. MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood 2006; 108:3472–3476.
Chaligné R, Tonetti C, Besancenot R, et al. New mutations of MPL in primitive myelofibrosis: only the MPL W515 mutations promote a G1/S-phase transition. Leukemia 2008; 22:1557–1566.
Scott LM, Tong W, Levine RL, et al. JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med 2007; 356:459–468.
Pardanani A, Lasho TL, Finke C, et al. Prevalence and clinicopathologic correlates of JAK2 exon 12 mutations in JAK2V617F negative polycythemia vera. Leukemia 2007; 21:1960–1963.
Martínez-Avilés L, Besses C, Alvarez-Larrán A, et al. JAK2 exon 12 mutations in polycythemia vera or idiopathic erythrocytosis. Haematologica 2007; 92:1717–1718.
Butcher CM, Hahn U, To LB, et al. Two novel JAK2 exon 12 mutations in JAK2V617F-negative polycythaemia vera patients. Leukemia 2008; 22:870–873.
Vardiman JW, Brunning RD, Harris NL. WHO histological classification of chronic myeloproliferative diseases. In: Jaffe ES, Harris NL, Stein H, Vardiman JW, eds. World Health Organization Classification of Tumors: Tumours of the Haematopoietic and Lymphoid Tissues. Lyon, France: International Agency for Research on Cancer (IARC) Press; 2001:17–44.
Zhang SJ, Li JY, Li WD, et al. The investigation of JAK2 mutation in Chinese myeloproliferative diseases-identification of a novel C616Y point mutation in a PV patient. Int J Lab Hematol 2007; 29:71–72.
Xu W, Li JY, Xia J, et al. MPL W515L mutation in Chinese patients with myeloproliferative diseases. Leuk Lymphoma 2008, 49:955–958.
Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 2002; 100:2292–2302.
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Xia, J., Lu, Mz., Jiang, Yq. et al. JAK2 V617F, MPL W515L and JAK2 exon 12 mutations in Chinese patients with primary myelofibrosis. Chin. J. Cancer Res. 24, 72–76 (2012). https://doi.org/10.1007/s11670-012-0072-4
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DOI: https://doi.org/10.1007/s11670-012-0072-4