Asian Pacific Journal of Cancer Prevention

  • 제17권10호
  • /
  • Pages.4647-4653
  • /
  • 2016
  • /
  • 1513-7368(pISSN)
  • /
  • 2476-762X(eISSN)
아시아태평양암예방학회 (Asian Pacific Journal of Cancer Prevention)
권호 표지
DOI QR코드

DOI QR Code

Characterization and Prognosis Significance of JAK2 (V617F), MPL, and CALR Mutations in Philadelphia-Negative Myeloproliferative Neoplasms

  • Singdong, Roongrudee (Human Genetic Laboratory, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University) ;
  • Siriboonpiputtana, Teerapong (Human Genetic Laboratory, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University) ;
  • Chareonsirisuthigul, Takol (Human Genetic Laboratory, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University) ;
  • Kongruang, Adcharee (Human Genetic Laboratory, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University) ;
  • Limsuwanachot, Nittaya (Human Genetic Laboratory, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University) ;
  • Sirirat, Tanasan (Department of Clinical Microscopy, Faculty of Medical Technology, Huacheiw Chalermprakiet University) ;
  • Chuncharunee, Suporn (Division of Hematology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University) ;
  • Rerkamnuaychoke, Budsaba (Human Genetic Laboratory, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University)
  • 발행 : 2016.10.01
⟨ 이전 논문 다음 논문 ⟩

초록

Background: The discovery of somatic acquired mutations of JAK2 (V617F) in Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPNs) including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) has not only improved rational disease classification and prognostication but also brings new understanding insight into the pathogenesis of diseases. Dosage effects of the JAK2 (V617F) allelic burden in Ph-negative MPNs may partially influence clinical presentation, disease progression, and treatment outcome. Material and Methods: Pyrosequencing was performed to detect JAK2 (V617F) and MPL (W515K/L) and capillary electrophoresis to identify CALR exon 9 mutations in 100 samples of Ph-negative MPNs (38.0 PV, 55 ET, 4 PMF, and 3 MPN-U). Results: The results showed somatic mutations of JAK2 (V617F) in 94.7% of PV, 74.5% of ET, 25.0% of PMF, and all MPN-U. A high proportion of JAK2 (V617F) mutant allele burden (mutational load > 50.0%) was predominantly observed in PV when compared with ET. Although a high level of JAK2 (V617F) allele burden was strongly associated with high WBC counts in both PV and ET, several hematological parameters (hemoglobin, hematocrit, and platelet count) were independent of JAK2 (V617F) mutational load. MPL (W515K/L) mutations could not be detected whereas CALR exon 9 mutations were identified in 35.7% of patients with JAK2 negative ET and 33.3% with JAK2 negative PMF. Conclusions: The JAK2 (V617F) allele burden may be involved in progression of MPNs. Furthermore, a high level of JAK2 (V617F) mutant allele appears strongly associated with leukocytosis in both PV and ET.

키워드

참고문헌

  1. Ahmed RZ, Rashid M, Ahmed N, Nadeem M, Shamsi TS (2016). Coexisting JAK2V617F and CALR exon 9 mutations in myeloproliferative neoplasms - Do they designate a new subtype? Asian Pac J Cancer Prev, 17, 923-6. https://doi.org/10.7314/APJCP.2016.17.3.923
  2. Arber DA, Orazi A, Hasserjian R, et al (2016). The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood, 127, 2391-405. https://doi.org/10.1182/blood-2016-03-643544
  3. Baxter EJ, Scott LM, Campbell PJ, et al (2005). Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet, 365, 1054-61. https://doi.org/10.1016/S0140-6736(05)74230-6
  4. Choi CW, Bang SM, Jang S, et al (2015). Guidelines for the management of myeloproliferative neoplasms. Korean J Intern Med, 30, 771-88. https://doi.org/10.3904/kjim.2015.30.6.771
  5. Duletic AN, Dekanic A, Hadzisejdic I, et al (2012). JAK2-v617F mutation is associated with clinical and laboratory features of myeloproliferative neoplasms. Coll Antropol, 36, 859-65
  6. Grinsztejn E, Percy MJ, McClenaghan D, et al (2016). The prevalence of CALR mutations in a cohort of patients with myeloproliferative neoplasms. Int J Lab Hematol, 38, 102-6. https://doi.org/10.1111/ijlh.12447
  7. Ha JS, Kim YK, Jung SI, et al (2012). Correlations between Janus kinase 2 V617F allele burdens and clinicohematologic parameters in myeloproliferative neoplasms. Ann Lab Med, 32, 385-91. https://doi.org/10.3343/alm.2012.32.6.385
  8. Huijsmans CJ, Poodt J, Savelkoul PH, et al (2011). Sensitive detection and quantification of the JAK2V617F allele by real-time PCR blocking wild-type amplification by using a peptide nucleic acid oligonucleotide. J Mol Diagn, 13, 558-64. https://doi.org/10.1016/j.jmoldx.2011.04.002
  9. Jekarl DW, Han SB, Kim M, et al (2010). JAK2 V617F mutation in myelodysplastic syndrome, myelodysplastic syndrome/myeloproliferative neoplasm, unclassifiable, refractory anemia with ring sideroblasts with thrombocytosis, and acute myeloid leukemia. Korean J Hematol, 45, 46-50. https://doi.org/10.5045/kjh.2010.45.1.46
  10. Jelinek J, Oki Y, Gharibyan V, et al (2005). JAK2 mutation 1849G>T is rare in acute leukemias but can be found in CMML, Philadelphia chromosome-negative CML, and megakaryocytic leukemia. Blood, 106, 3370-3. https://doi.org/10.1182/blood-2005-05-1800
  11. Jones AV, Kreil S, Zoi K, et al (2005). Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders. Blood, 106, 2162-8. https://doi.org/10.1182/blood-2005-03-1320
  12. Kim JT, Cho YG, Choi SI, et al (2010). JAK2 V617F and exon 12 geneticvariations in Korean patients with BCR/ABL1-negative myeloproliferative neoplasms. Korean J Lab Med, 30, 567-74. https://doi.org/10.3343/kjlm.2010.30.6.567
  13. Kim BH, Cho YU, Bae MH, et al (2015a). JAK2 V617F, MPL, and CALR mutations in Korean patients with essential thrombocythemia and primary myelofibrosis. J Korean Med Sci, 30, 882-8. https://doi.org/10.3346/jkms.2015.30.7.882
  14. Kim SY, Im K, Park SN, et al (2015b). CALR, JAK2, and MPL mutation profiles in patients with four different subtypes of myeloproliferative neoplasms: primary myelofibrosis, essential thrombocythemia, polycythemia vera, and myeloproliferative neoplasm, unclassifiable. Am J Clin Pathol, 143, 635-44. https://doi.org/10.1309/AJCPUAAC16LIWZMM
  15. Klampfl T, Gisslinger H, Harutyunyan AS, et al (2013). Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med, 369, 2379-90. https://doi.org/10.1056/NEJMoa1311347
  16. Lakey MA, Pardonani A, Hoyer JD, et al (2010). Bone marrow morphologic features in polycythemia vera with JAK2 exon 12 mutations. Am J Clin Pathol, 133, 942-8. https://doi.org/10.1309/AJCP3Z2AKUWRGTNM
  17. Larsen TS, Pallisgaard N, Moller MB, Hasselbalch HC (2007). The JAK2 V617F allele burden in essential thrombocythemia, polycythemia vera and primary myelofibrosis--impact on disease phenotype. Eur J Haematol, 79, 508-15. https://doi.org/10.1111/j.1600-0609.2007.00960.x
  18. Levine RL, Wadleigh M, Cools J, et al (2005). Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell, 7, 387-97. https://doi.org/10.1016/j.ccr.2005.03.023
  19. Lin Y, Liu E, Sun Q, et al (2015). The prevalence of JAK2, MPL, and CALR mutations in Chinese patients with BCR-ABL1-negative myeloproliferative neoplasms. Am J Clin Pathol, 144, 165-71. https://doi.org/10.1309/AJCPALP51XDIXDDV
  20. Nangalia J, Massie CE, Baxter EJ, et al (2013). Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med, 369, 2391-405. https://doi.org/10.1056/NEJMoa1312542
  21. Pardanani AD, Levine RL, Lasho T, et al (2006). MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood, 108, 3472-6. https://doi.org/10.1182/blood-2006-04-018879
  22. Rampal R, Al-Shahrour F, Abdel-Wahab O, et al (2014). Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis. Blood, 123, 123-33. https://doi.org/10.1182/blood-2014-02-554634
  23. Ruan GR, Jiang B, Li LD, et al (2010). MPL W515L/K mutations in 343 Chinese adults with JAK2V617F mutation-negative chronic myeloproliferative disorders detected by a newly developed RQ-PCR based on TaqMan MGB probes. Hematol Oncol, 28, 33-9.
  24. Rumi E, Harutyunyan AS, Pietra D, et al (2014). CALR exon 9 mutations are somatically acquired events in familial cases of essential thrombocythemia or primary myelofibrosis. Blood, 123, 2416-9. https://doi.org/10.1182/blood-2014-01-550434
  25. Sultan S, Irfan SM (2015a). Acquired JAK-2 V617F mutational analysis in Pakistani patients with essential thrombocythemia. Asian Pac J Cancer Prev, 16, 7327-30. https://doi.org/10.7314/APJCP.2015.16.16.7327
  26. Sultan S, Irfan SM (2015b). JAK-2 V617F mutational analysis in primary idiopathic myelofibrosis: experience from Southern Pakistan. Asian Pac J Cancer Prev, 16, 7889-92. https://doi.org/10.7314/APJCP.2015.16.17.7889
  27. Sultan S, Irfan SM, Khan SR (2016). Somatic JAK-2 V617F mutational analysis in polycythemia rubra vera: a tertiary care center experience. Asian Pac J Cancer Prev, 17, 1053-5. https://doi.org/10.7314/APJCP.2016.17.3.1053
  28. Scott LM, Tong W, Levine RL, et al (2007). JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med, 356, 459-68. https://doi.org/10.1056/NEJMoa065202
  29. Tefferi A, Wassie EA, Lasho TL, et al (2014a). Calreticulin mutations and long-term survival in essential thrombocythemia. Leukemia, 28, 2300-3. https://doi.org/10.1038/leu.2014.148
  30. Tefferi A, Lasho TL, Finke CM, et al (2014b). CALR vs JAK2 vs MPL-mutated or triple-negative myelofibrosis: clinical, cytogenetic and molecular comparisons. Leukemia, 28, 1472-7. https://doi.org/10.1038/leu.2014.3
  31. Vainchenker W, Delhommeau F, Constantinescu SN, Bernard OA (2011). New mutations and pathogenesis of myeloproliferative neoplasms. Blood, 118, 1723-35. https://doi.org/10.1182/blood-2011-02-292102
  32. Vardiman JW, Thiele J, Arber DA, et al (2009). The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood, 114, 937-51. https://doi.org/10.1182/blood-2009-03-209262