Overview of Myeloproliferative Neoplasms (Also Known as Myeloproliferative Disorders)

Essential Thrombocythemia, Polycythemia Vera, and Myelofibrosis Are Characterized by Increased Proliferation of Myeloid, Megakaryocytic, and Erythroid Cells

Myeloproliferative neoplasms (MPNs), which are also known as myeloproliferative disorders (MPDs), share molecular and cellular characteristics but differ in phenotype and clinical presentation.1-3 Essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF) are 3 Philadelphia chromosome−negative [Ph(−)] MPNs characterized by increased clonal proliferation of myeloid cells.4 In these myeloproliferative disorders, unregulated proliferation may occur in 1 or more myeloid cell lines, including erythrocytes, platelets, and granulocytes.5,6

chart depicts the phenotype of myeloproliferative neoplasms disorders and the corresponding disease such as myelofibrosis, polycythemia vera (PV) and essential thombocythemia

Overactive JAK Pathway Signaling Is a Key Mechanism of Disease in MPNs7,8

Well-regulated JAK signaling is essential for cell production, cell proliferation, and immune function. Intracellular regulators, such as suppressor of cytokine signaling (SOCS), help regulate JAK signaling.7,9

Cytokines bind to receptors and activate JAKs. JAKs activate signal transducers and activators of transcriptions (STATs), which dimerize and enter the nucleus. Inside the nucleus, the STATs bind to DNA, stimulating the expression of genes related to cell survival, differentiation, and proliferation.7,10-12

Factors that impact JAK signaling8,9,13-19:

  • JAK2 mutations
  • MPL mutations
  • Excess cytokines
  • Increased JAK1 signaling
  • Impaired negative signaling mechanisms (eg, those involving SOCS)
JAK = Janus-associated kinase MPL = myeloproliferative leukemia virus oncogene STAT = signal transducer and activator of transcription
image shows a cell with normal signaling and overactive signaling
References

1. Vannucchi AM, Guglielmelli P, Tefferi A. CA Cancer J Clin. 2009;59:171-191. 2. Tefferi A, Vardiman JW. Leukemia. 2008;22:14-22. 3. Verstovsek S. Clin Cancer Res. 2010;16:1988-1996. 4. Arber DA, Orazi A, Hasserjian R, et al. Blood. 2016;127(20):2391-2405. 5. Delhommeau F, Jeziorowska D, Marzac C, Casadevall N. Int J Hematol. 2010;91:165-173. 6. Spivak JL. Ann Intern Med. 2010;152:300-306. 7. Furqan M, Mukhi N, Lee B, Liu D. Biomarker Res. 2013:1:1-10. 8. Quintás-Cardama A, Vaddi K, Liu P, et al. Blood. 2010;115:3109-3117. 9. Fourouclas N, Li J, Gilby DC, et al. Haematologica. 2008;93(11):1635-1644. 10. Kisseleva T, Bhattacharya S, Braunstein J, et al. Gene. 2002;285(1-2):1-24. 11. Pellegrini S, Dusanter-Fourt I. Eur J Biochem. 1997;248(3):615-633. 12. Quintás-Cardama A, Kantarjian H, Cortes J, et al. Nat Rev Drug Discov. 2011;10(2):127-140. 13. Kralovics R, Passamonti F, Buser AS, et al. N Engl J Med. 2005;352(17):1779-1790. 14. Chaligné R, Tonetti C, Besancenot R, et al. Leukemia. 2008;22(8):1557-1566. 15. Scott LM, Tong W, Levine RL, et al. N Engl J Med. 2007;356(5):459-468. 16. Pikman Y, Lee BH, Mercher T, et al. PLoS Med. 2006;3(7):e270. 17. Kralovics R. Leukemia. 2008;22(10):1841-1848. 18. Tefferi A, Vaidya R, Caramazza D, Finke C, Lasho T, Pardanani A. J Clin Oncol. 2011;29(10):1356-1363. 19. Verstovsek S. Hematology Am Soc Hematol Educ Program. 2009:636-642.

 
Resources
By: World Health Organization (WHO)
A diagnostic worksheet from the WHO for primary MF, PV, and ET.
By: International Working Group for Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)
Diagnostic criteria from the IWG-MRT.
By: MPN Connect
NCCN-recommended tool for assessing symptom burden.