Current Hematologic Malignancy Reports

, Volume 14, Issue 5, pp 376–385 | Cite as

Philadelphia-Negative Myeloproliferative Neoplasms: Laboratory Workup in the Era of Next-Generation Sequencing

  • Zhuang Zuo
  • Shaoying Li
  • Jie Xu
  • M. James You
  • Joseph D. Khoury
  • C. Cameron YinEmail author
Molecular Testing and Diagnostics (J Khoury, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Molecular Testing and Diagnostics


Purpose of Review

To review the impact of next-generation sequencing (NGS) on laboratory approach of myeloproliferative neoplasms (MPNs).

Recent Findings

Next-generation sequencing has provided valuable information on the mutational landscape of MPNs and has been used for various applications, including diagnosis, risk stratification, monitoring of residual disease or disease progression, and target therapy. Most commonly, targeted sequencing of a panel of genes that have been shown to be recurrently mutated in myeloid neoplasms is used. Although numerous studies have shown the benefit of using NGS in the routine clinical care of MPN patients, the complexity of NGS data and how these data may contribute to the clinical outcome have limited the development of a standard clinical guideline.


We review recent literature and discuss how to interpret and use NGS data in the clinical care of MPN patients.


Next-generation sequencing Myeloproliferative neoplasms Polycythemia vera Essential thrombocythemia Primary myelofibrosis Chronic neutrophilic leukemia 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005;365(9464):1054–61.PubMedGoogle Scholar
  2. 2.
    James C, Ugo V, Le Couedic JP, Staerk J, Delhommeau F, Lacout C, et al. A unique clonal JAK2 mutation leading to constitutive signaling causes polycythaemia vera. Nature. 2005;434(7037):1144–8.PubMedGoogle Scholar
  3. 3.
    Jones AV, Kreil S, Zoi K, Waghorn K, Curtis C, Zhang L, et al. Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders. Blood. 2005;106(6):2162–8.PubMedGoogle Scholar
  4. 4.
    Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005;352(17):1779–90.PubMedGoogle Scholar
  5. 5.
    Levine RL, Wadleigh M, Cools J, Ebert BL, Wernig G, Huntly BJ, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. 2005;7(4):387–97.PubMedGoogle Scholar
  6. 6.
    Pardanani A, Lasho TL, Finke C, Hanson CA, Tefferi A. Prevalence and clinicopathologic correlates of JAK2 exon 12 mutations in JAK2V617F-negative polycythemia vera. Leukemia. 2007;21(9):1960–3.PubMedGoogle Scholar
  7. 7.
    Scott LM, Tong W, Levine RL, Scott MA, Beer PA, Stratton MR, et al. JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med. 2007;356(5):459–68.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Lasho TL, Pardanani A, Tefferi A. LNK mutations in JAK2 mutation-negative erythrocytosis. N Engl J Med. 2010;363(12):1189–90.PubMedGoogle Scholar
  9. 9.
    Oh ST, Simonds EF, Jones C, Hale MB, Goltsev Y, Gibbs KD, et al. Novel mutations in the inhibitory adaptor protein LNK drive JAK-STAT signaling in patients with myeloproliferative neoplasms. Blood. 2010;116(6):988–92.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Pardanani A, Lasho T, Finke C, Oh ST, Gotlib J, Tefferi A. LNK mutation studies in blast-phase myeloproliferative neoplasms, and in chronic-phase disease with TET2, IDH, JAK2 or MPL mutations. Leukemia. 2010;24(10):1713–8.PubMedGoogle Scholar
  11. 11.
    Grand FH, Hidalgo-Curtis CE, Emst T, Zoi K, Zoi C, McGuire C, et al. Frequent CBL mutations associated with 11q acquired uniparental disomy in myeloproliferative neoplasms. Blood. 2009;113(24):6182–92.PubMedGoogle Scholar
  12. 12.
    Sanada M, Suzuki T, Shih LY, Otsu M, Kato M, Yamazaki S, et al. Gain-of-function of mutated C-CBL tumor suppressor in myeloid neoplasms. Nature. 2009;460(7257):904–8.PubMedGoogle Scholar
  13. 13.
    Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med. 2013;369(25):2379–90.PubMedGoogle Scholar
  14. 14.
    Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med. 2013;369(25):2391–405.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Pardanani AD, Levine RL, Lasho T, Pikman Y, Mesa RA, Wadleigh M, et al. MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood. 2006;108(10):3472–6.PubMedGoogle Scholar
  16. 16.
    Pikman Y, Lee BH, Mercher T, McDowell E, Ebert BL, Gozo M, et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med. 2006;3(7):e270.PubMedPubMedCentralGoogle Scholar
  17. 17.
    Tefferi A, Pardanani A. Myeloproliferative neoplasms: a contemporary review. JAMA Oncol. 2015;1(1):97–105.PubMedGoogle Scholar
  18. 18.
    Ortmann CA, Kent DG, Nangalia J, Silber Y, Wedge DC, Grinfeld J, et al. Effect of mutation order on myeloproliferative neoplasms. N Engl J Med. 2015;372(7):601–12.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Vannucchi AM, Antonioli E, Guglielmelli P, Longo G, Pancrazzi A, Ponziani V, et al. Prospective identification of high-risk polycythemia vera patients based on JAK2(V617F) allele burden. Leukemia. 2007;21(9):1952–9.PubMedGoogle Scholar
  20. 20.
    Yao H, Ma Y, Hong Z, Zhao L, Monaghan SA, Hu MC, et al. Activating JAK2 mutants reveal cytokine receptor coupling differences that impact outcomes in myeloproliferative neoplasm. Leukemia. 2017;31(10):2122–31.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Levine RL, Loriaux M, Huntly BJ, Loh ML, Beran M, Stoffregen E, 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(10):3377–9.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Atallah E, Nussenzveig R, Yin CC, Bueso-Ramos C, Tam C, Manshouri T, et al. Prognostic interaction between thrombocytosis and JAK2 V617F mutation in the WHO subcategories of myelodysplastic/myeloproliferative disease-unclassifiable and refractory anemia with ringed sideroblasts and marked thrombocytosis. Leukemia. 2008;22(6):1295–8.PubMedGoogle Scholar
  23. 23.
    Gur HD, Loghavi S, Garcia-Manero G, Routbort M, Kanagal-Shamanna R, Quesada A, et al. Chronic myelomonocytic leukemia with fibrosis is a distinct disease subset with myeloproliferative features and frequent JAK2 V617F mutations. Am J Surg Pathol. 2018;42(6):799–806.PubMedGoogle Scholar
  24. 24.
    Steensma DP, Bejar R, Jalswal S, Lindsley RC, Sekeres MA, Hasserjian RP, et al. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood. 2015;126(1):9–16.PubMedPubMedCentralGoogle Scholar
  25. 25.
    Gold LI, Eggleton P, Sweetwyne MT, Van Duyn LB, Greives MR, Naylor SM, et al. Calreticulin: non-endoplasmic reticulum functions in physiology and disease. FASEB J. 2010;24(3):665–83.PubMedPubMedCentralGoogle Scholar
  26. 26.
    Elf S, Abdelfattah NS, Chen E, Perales-Paton J, Rosen EA, Ko A, et al. Mutant calreticulin requires both its mutant C-terminus and the thrombopoietin receptor for oncogenic transformation. Cancer Discov. 2016;6(4):368–81.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Chachoua I, Pecquet C, El-Khoury M, Nivarthi H, Albu RI, Marty C, et al. Thrombopoietin receptor activation by myeloproliferative neoplasm associated calreticulin mutants. Blood. 2016;127(10):1325–35.PubMedGoogle Scholar
  28. 28.
    Rotunno G, Mannarelli C, Guglielmelli P, Pacilli A, Pancrazzi A, Pieri L, et al. Impact of calreticulin mutations on clinical and hematological phenotype and outcome in essential thrombocythemia. Blood. 2014;123(10):1552–5.PubMedGoogle Scholar
  29. 29.
    Tefferi A, Lasho TL, Finke C, Belachew AA, Wassie EA, Ketterling RP, et al. Type I vs type 2 calreticulin mutations in primary myelofibrosis: differences in phenotype and prognostic impact. Leukemia. 2014;28(7):1568–70.PubMedGoogle Scholar
  30. 30.
    Tefferi A, Lasho TL, Tischer A, Wassie EA, Finke CM, Belachew AA, et al. The prognostic advantage of calreticulin mutations in myelofibrosis might be confined to type 1 or type 1-like CALR variants. Blood. 2014;24(15):2465–6.Google Scholar
  31. 31.
    Tefferi A, Nicolosi M, Mudireddy M, Szuber N, Finke CM, Lasho TL, et al. Driver mutations and prognosis in primary myelofibrosis: Mayo-Careggi MPN alliance study of 1095 patients. Am J Hematol. 2018;93(3):348–55.PubMedGoogle Scholar
  32. 32.
    Vannucchi AM, Antonioli E, Guglielmelli P, Pancrazzi A, Guerini V, Barosi G, et al. Characteristics and clinical correlates of MPL 515W>L/K mutation in essential thrombocythemia. Blood. 2008;112(3):844–7.PubMedGoogle Scholar
  33. 33.
    Haider M, Elala YC, Gangat N, Hanson CA, Tefferi A. MPL mutations and palpable splenomegaly are independent risk factors for fibrotic progression in essential thrombocythemia. Blood Cancer J. 2016;6(10):e487.PubMedPubMedCentralGoogle Scholar
  34. 34.
    Cabagnols X, Favale F, Pasquier F, Messaoudi K, Defour JP, Ianotto JC, et al. Presence of atypical thrombopoietin receptor (MPL) mutations in triple-negative essential thrombocythemia patients. Blood. 2016;127(3):333–42.PubMedGoogle Scholar
  35. 35.
    Milosevic Feenstra JD, Nivarthi H, Gisslinger H, Leroy E, Rumi E, Chachoua I, et al. Whole-exome sequencing identifies novel MPL and JAK2 mutations in triple-negative myeloproliferative neoplasms. Blood. 2016;127(3):325–32.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Rumi E, Pietra D, Pascutto C, Guglielmelli P, Martinez-Trillos A, Casetti I, et al. Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis. Blood. 2014;124(7):1062–9.PubMedPubMedCentralGoogle Scholar
  37. 37.
    Li B, Zhang L, Bai J, Xu Z, Qin T, Zhang Y, et al. Non-driver mutations profile identified by a 206-gene NGS panel in patients with primary myelofibrosis and post-polycythaemia/essential thrombocythaemia myelofibrosis in a single center from China. Blood. 2016;128(22):1942.Google Scholar
  38. 38.
    Tefferi A, Lasho TL, Finke CM, Elala Y, Hanson CA, Kettering RP, et al. Targeted deep sequencing in primary myelofibrosis. Blood Adv. 2016;1(2):105–11.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Tefferi A, Lasho TL, Guglielmelli P, Finke CM, Rotunno G, Elala Y, et al. Targeted deep sequencing in polycythemia vera and essential thrombocythemia. Blood Adv. 2016;1(1):21–30.PubMedPubMedCentralGoogle Scholar
  40. 40.
    Delhommeau F, Dupont S, Della Valle V, James C, Trannoy S, Masse A, et al. Mutation in TET2 in myeloid cancers. N Engl J Med. 2009;360(22):2289–301.PubMedGoogle Scholar
  41. 41.
    Lundberg P, Larow A, Nienhold R, Looser R, Hao-Shen H, Nissen I, et al. Clonal evolution and clinical correlates of somatic mutations in myeloproliferative neoplasms. Blood. 2014;123(14):2220–8.PubMedGoogle Scholar
  42. 42.
    Tefferi A, Pardanani A, Lim KH, Abdel-Wahab O, Lasho TL, Patel J, et al. TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myolofibrosis. Leukemia. 2009;23(5):905–11.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Cerquozzi S, Baraco D, Lasho T, Finke C, Hanson CA, Ketterling RP, et al. Risk factors for arterial versus venous thrombosis in polycythemia vera: a single center experience in 587 patients. Blood Cancer J. 2017;7(12):662.PubMedPubMedCentralGoogle Scholar
  44. 44.
    Stegelmann F, Bullinger L, Schlenk RF, Paschka P, Griesshammer M, Blersch C, et al. DNMT3A mutations in myeloproliferative neoplasms. Leukemia. 2011;25(7):1217–9.PubMedGoogle Scholar
  45. 45.
    Jacquelin S, Straube J, Cooper L, Vu T, Song Z, Bywater M, et al. Jak2V617F and Dnmt3a cooperate to induce myelofibrosis through activated enhancer-driven inflammation. Blood. 2018;132(26):2707–21.PubMedGoogle Scholar
  46. 46.
    Nangalia J, Nice FL, Wedge DC, Godfrey AL, Grinfeld J, Thakker C, et al. DNMT3A mutations occur early or late in patients with myeloproliferative neoplasms and mutation order influence phenotype. Haematologica. 2015;100(11):e438–42.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Pardanani A, Lasho TL, Finke CM, Mai M, McClure RF, Tefferi A. IDH1 and IDH2 mutation analysis in chronic- and blast-phase myeloproliferative neoplasms. Leukemia. 2010;24(6):1146–51.PubMedGoogle Scholar
  48. 48.
    Tefferi A, Lasho TL, Abdel-Wahab O, Guglielmelli P, Patel J, Caramazza D, et al. IDH1 and IDH2 mutation studies in 1473 patients with chronic-, fibrotic-, or blast-phase essential thrombocythemia, polycythemia vera or myelofibrosis. Leukemia. 2010;24(7):1302–9.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Gross S, Cairns RA, Minden MD, Driggers EM, Bittinger MA, Jang HG, et al. Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations. J Exp Med. 2010;207(2):339–44.PubMedPubMedCentralGoogle Scholar
  50. 50.
    Tefferi A, Jimma T, Sulai NH, Lasho TL, Finke CM, Knudson RA, et al. IDH mutations in primary myelofibrosis predict leukemic transformation and shortened survival: clinical evidence for leukemogenic collaboration with JAK2V617F. Leukemia. 2012;26(3):475–80.PubMedPubMedCentralGoogle Scholar
  51. 51.
    Yonal-Hindilergen I, Daglar-Aday A, Hindilerden F, Akadam-Teker B, Yilmaz C, Nalcaci M, et al. The clinical significance of IDH mutations in essential thrombocythemia and primary myelofibrosis. J Clin Med Res. 2016;8(1):29–39.Google Scholar
  52. 52.
    Wong WJ, Hasserjian RP, Pinkus GS, Breyfogle LJ, Mullally A, Pozdnyakova O. JAK2, CALR, MPL and ASXL1 mutational status correlates with distinct histological features in Philadelphia chromosome-negative myeloproliferative neoplasms. Haematologica. 2018;103(2):e63–8.PubMedPubMedCentralGoogle Scholar
  53. 53.
    Triviai I, Zeschke S, Rentel J, Spanakis M, Scherer T, Gabdoulline R, et al. ASXL1/EZH2 mutations promote clonal expansion of neoplastic HSC and impair erythropoiesis in PMF. Leukemia. 2019;33(1):99–109.PubMedGoogle Scholar
  54. 54.
    Abdel-Wahab O, Pardanani A, Patel J, Wadleigh M, Lasho T, Heguy A, et al. Concomitant analysis of EZH2 and ASXL1 mutations in myelofibrosis, chronic myelomonocytic leukemia and blast-phase myeloproliferative neoplasms. Leukemia. 2011;25(7):1200–2.PubMedPubMedCentralGoogle Scholar
  55. 55.
    Guglielmelli P, Biamonte F, Score J, Hidalgo-Curtis C, Cervantes F, Maffioli M, et al. EZH2 mutational status predicts poor survival in myelofibrosis. Blood. 2011;118(19):5227–34.PubMedGoogle Scholar
  56. 56.
    Tefferi A, Guglielmelli P, Lasho TL, Rotunno G, Finke C, Mannarelli C, et al. CALR and ASXL1 mutations-based molecular prognostication in primary myelofibrosis: an international study of 570 patients. Leukemia. 2014;28(7):1494–500.PubMedGoogle Scholar
  57. 57.
    McNamara CJ, Panzarella T, Kennedy JA, Arruda A, Claudio JD, Daher-Reyes G, et al. The mutational landscape of accelerated- and blast-phase myeloproliferative neoplasms impacts patient outcomes. Blood Adv. 2018;2(20):2658–71.PubMedPubMedCentralGoogle Scholar
  58. 58.
    Zhang S, Rampal R, Manshouri T, Patel J, Mensah N, Kayserian A, et al. Genetic analysis of patients with leukemic transformation of myeloproliferative neoplasms shows recurrent SRSF2 mutations that are associated with adverse outcome. Blood. 2012;119(19):4480–5.PubMedPubMedCentralGoogle Scholar
  59. 59.
    Yoshida K, Sanada M, Shiraishi Y, Nowak D, Nagata Y, Yamamoto R, et al. Frequent pathway mutations of splicing machinery in myelodysplasia. Nature. 2011;478(7367):64–9.PubMedGoogle Scholar
  60. 60.
    Lasho TL, Jimma T, Finke CM, Patnaik M, Hanson CA, Ketterling RP, et al. SRSF2 mutations in primary myelofibrosis: significant clustering with IDH mutations and independent association with inferior overall and leukemia-free survival. Blood. 2012;120(2):4168–71.PubMedGoogle Scholar
  61. 61.
    Boiocchi L, Hasserjian RP, Pozdnyakova O, Wong WJ, Lennerz JK, Le LP, et al. Clinicopathological and molecular features of SF3B1-mutated myeloproliferative neoplasms. Hum Pathol. 2019;86:1–11.PubMedGoogle Scholar
  62. 62.
    Lasho TL, Mudireddy M, Finke CM, Hanson CA, Ketterling RP, Szuber N, et al. Targeted next-generation sequencing in blast phase myeloproliferative neoplasms. Blood Adv. 2018;2(4):370–80.PubMedPubMedCentralGoogle Scholar
  63. 63.
    Maxson JE, Gotlib J, Pollyea DA, Fleischman AG, Agarwal A, Eide CA, et al. Oncogenic CSF3R mutations in chronic neutrophilic leukemia and atypical CML. N Engl J Med. 2013;368(19):1781–90.PubMedPubMedCentralGoogle Scholar
  64. 64.
    Pardanani A, Lasho TL, Laborde RR, Elliott M, Hanson CA, Knudson RA, et al. CSF3R T618I is a highly prevalent and specific mutation in chronic neutrophilic leukemia. Leukemia. 2013;27(9):1870–3.PubMedPubMedCentralGoogle Scholar
  65. 65.
    Meggendorfer M, Haferlach T, Alpermann T, Jeromin S, Haferlach C, Kern W, et al. Specific molecular mutation patterns delineate chronic neutrophilic leukemia, atypical chronic myeloid leukemia, and chronic myelomonocytic leukemia. Haematologica. 2014;99(12):e244–6.PubMedPubMedCentralGoogle Scholar
  66. 66.
    Elliott MA, Pardanani A, Hanson CA, Lasho TL, Finke CM, Belachew AA, et al. ASXL1 mutations are frequent and prognostically detrimental in CSF3R-mutated chronic neutrophilic leukemia. Am J Hematol. 2015;90(7):653–6.PubMedGoogle Scholar
  67. 67.
    Nooruddin Z, Miltgen N, Wei Q, Schowinsky J, Pan Z, Tobin J, et al. Changes in allele frequencies of CSF3R and SETBP1 mutations and evidence of clonal evolution in a chronic neutrophilic leukemia patient treated with ruxolitinib. Haematologica. 2017;102(5):e207–9.PubMedPubMedCentralGoogle Scholar
  68. 68.
    Vannucchi AM, Lasho TL, Guglielmelli P, Biamonte F, Pardanani A, Pereira A, et al. Mutations and prognosis in primary myelofibrosis. Leukemia. 2013;27(9):1861–9.PubMedGoogle Scholar
  69. 69.
    • Guglielmelli P, Lasho TL, Rotunno G, Mudireddy M, Mannarelli C, Nicolosi M, et al. MIPSS70: mutation-enhanced international prognostic score system for transplantation-age patients with primary myelofibrosis. J Clin Oncol. 2018;36(4):310–8 The authors developed a novel prognostic model for transplantation-age patients with primary myelofibrosis that integrates clinical, cytogenetic, and molecular data. The three-tiered MIPSS70 score reliably identified high-risk patients who may benefit from upfront use of allogeneic stem cell transplantation. PubMedGoogle Scholar
  70. 70.
    Guglielmelli P, Lasho TL, Rotunno G, Score J, Mannarelli C, Pancrazzi A, et al. The number of prognostically detrimental mutations and prognosis in primary myelofibrosis: an international study of 797 patients. Leukemia. 2014;28(9):1804–10.PubMedGoogle Scholar
  71. 71.
    Tefferi A, Guglielmelli P, Nicolos M, Mannelli F, Mudireddy M, Bartalucci N, et al. GIPSS: genetically inspired prognostic scoring system for primary myelofibrosis. Leukemia. 2018;32(7):1631–42.PubMedPubMedCentralGoogle Scholar
  72. 72.
    • Passamonti F, Giorgino T, Mora B, Guglielmelli P, Rumi E, Maffioli M, et al. A clinical-molecular prognostic model to predict survival in patients with post polycythemia vera and post essential thrombocythemia myelofibrosis. Leukemia. 2017;31(12):2726–31 The authors developed an integrated clinical-molecular prognostic model to predict survival in myelofibrosis secondary to polycythemia vera and essential thrombocythemia (MYSEC-PM). PubMedGoogle Scholar
  73. 73.
    •• Grinfeld J, Nangalia J, Baxter EJ, Wedge DC, Angelopoulos N, Cantrill R, et al. Classification and personalized prognosis in myeloprolfierative neoplasms. N Engl J Med. 2018;379(15):1416–30 The authors performed comprehensive genomic characterization of MPNs and identified eight genetic subgroups with distinct clinical phenotypes, risk of leukemic transformation, and event-free survival. This new genomic classification and prognostic model shows promise for personalized risk stratification and treatment. PubMedGoogle Scholar
  74. 74.
    Li S, Yin CC. Myelodysplastic syndrome. In: Chang C, Ohgami RS (eds) Precision molecular pathology of myeloid neoplasms. Springer; 2018. p 83–98.Google Scholar
  75. 75.
    van der Velden VH, Hochhaus A, Cazzaniga G, Szczepanski T, Gabert J, van Dongen JJ. Detection of minimal residual disease in hematologic malignancies by real-time quantitative PCR: principles, approaches, and laboratory aspects. Leukemia. 2003;17(6):1013–34.PubMedGoogle Scholar
  76. 76.
    Verstovsek S, Gotlib J, Mesa RA, Vannucchi AM, Kiladjian JJ, Cervantes F, et al. Long-term survival in patients treated with ruxolitinib for myelofibrosis: COMFORT-I and -II pooled analyses. J Hematol Oncol. 2017;10(1):156.PubMedPubMedCentralGoogle Scholar
  77. 77.
    Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012;366(9):799–807.PubMedPubMedCentralGoogle Scholar
  78. 78.
    Schlenk RF, Stegelmann F, Reiter A, Jost E, Gattermann N, Hebart H, et al. Pomalidomide in myeloproliferative neoplasm-associated myelofibrosis. Leukemia. 2017;31(4):889–95.PubMedGoogle Scholar
  79. 79.
    McKenney AS, Lau AN, Somasundara AVH, Spitzer B, Intlekofer AM, Ahn J, et al. JAK2/IDH-mutant-driven myeloproliferative neoplasm is sensitive to combined targeted inhibition. J Clin Invest. 2018;128(2):789–804.PubMedPubMedCentralGoogle Scholar
  80. 80.
    Chang Y, Lin H, Chiang Y, Chen CG, Huang L, Wang W, et al. Targeted next-generation sequencing identified novel mutations in triple-negative myeloproliferative neoplasms. Med Oncol. 2017;34(5):83.PubMedGoogle Scholar
  81. 81.
    Patel KP, Ruiz-Cordero R, Chen W, Routbort MJ, Floyd K, Rodriguez S, et al. Ultra-rapid reporting of genomic targets (URGENTseq): clinical next-generation sequencing results within 48 hours of sample collection. J Mold Diagn. 2019;2(1):89–98.Google Scholar
  82. 82.
    Rampai R, Ahn J, Abdel-Wahab O, Nahas M, Wang K, Lipson D, et al. Genomic and functional analysis of leukemic transformation of myeloproliferative neoplasms. Proc Natl Acad Sci U S A. 2014;111(50):E5401–10.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Zhuang Zuo
    • 1
  • Shaoying Li
    • 1
  • Jie Xu
    • 1
  • M. James You
    • 1
  • Joseph D. Khoury
    • 1
  • C. Cameron Yin
    • 1
    Email author
  1. 1.Department of HematopathologyUniversity of Texas MD Anderson Cancer CenterHoustonUSA

Personalised recommendations