Chronic Myeloproliferative Neoplasms Treatment (PDQ®)–Health Professional Version

General Information About Chronic Myeloproliferative Neoplasms (MPN)

The chronic MPN consist of chronic myelogenous leukemia, polycythemia vera (p. vera), primary myelofibrosis, essential thrombocythemia, chronic neutrophilic leukemia, and chronic eosinophilic leukemia. All of these disorders involve dysregulation at the multipotent hematopoietic stem cell (CD34), with one or more of the following shared features:

  • Overproduction of one or several blood elements with dominance of a transformed clone.
  • Hypercellular marrow/marrow fibrosis.
  • Cytogenetic abnormalities.
  • Thrombotic and/or hemorrhagic diatheses.
  • Extramedullary hematopoiesis (liver/spleen).
  • Transformation to acute leukemia.
  • Overlapping clinical features.

Chronic MPN usually occur sporadically; however, familial clusters of MPN have been reported. These familial clusters include autosomal-dominant inheritance and autosomal-recessive inheritance.[1] Patients with p. vera and essential thrombocythemia have marked increases of red blood cell and platelet production, respectively. Treatment is directed at reducing the excessive numbers of blood cells. Both p. vera and essential thrombocythemia can develop a spent phase late in their courses that resembles primary myelofibrosis with cytopenias and marrow hypoplasia and fibrosis.[2-4] A specific point mutation in one copy of the Janus kinase 2gene (JAK2), a cytoplasmic tyrosine kinase, on chromosome 9, which causes increased proliferation and survival of hematopoietic precursors in vitro, has been identified in most patients with p. vera, essential thrombocythemia, and idiopathic myelofibrosis.[5-10] Researchers are pursuing specific targeting of this aberrant protein. Other somatic activating mutations have been identified, including the myeloproliferative leukemia (MPL) exon 10 and the calreticulin (CALR) gene in patients with essential thrombocythemia and primary myelofibrosis.[11-13]

  1. Ranjan A, Penninga E, Jelsig AM, et al.: Inheritance of the chronic myeloproliferative neoplasms. A systematic review. Clin Genet 83 (2): 99-107, 2013. [PUBMED Abstract]
  2. Schafer AI: Bleeding and thrombosis in the myeloproliferative disorders. Blood 64 (1): 1-12, 1984. [PUBMED Abstract]
  3. Barosi G: Myelofibrosis with myeloid metaplasia: diagnostic definition and prognostic classification for clinical studies and treatment guidelines. J Clin Oncol 17 (9): 2954-70, 1999. [PUBMED Abstract]
  4. Tefferi A: Myelofibrosis with myeloid metaplasia. N Engl J Med 342 (17): 1255-65, 2000. [PUBMED Abstract]
  5. Kralovics R, Passamonti F, Buser AS, et al.: A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 352 (17): 1779-90, 2005. [PUBMED Abstract]
  6. Baxter EJ, Scott LM, Campbell PJ, et al.: Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 365 (9464): 1054-61, 2005 Mar 19-25. [PUBMED Abstract]
  7. James C, Ugo V, Le Couédic JP, et al.: A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 434 (7037): 1144-8, 2005. [PUBMED Abstract]
  8. 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. Cancer Cell 7 (4): 387-97, 2005. [PUBMED Abstract]
  9. Scott LM, Tong W, Levine RL, et al.: JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med 356 (5): 459-68, 2007. [PUBMED Abstract]
  10. Campbell PJ, Green AR: The myeloproliferative disorders. N Engl J Med 355 (23): 2452-66, 2006. [PUBMED Abstract]
  11. Cazzola M, Kralovics R: From Janus kinase 2 to calreticulin: the clinically relevant genomic landscape of myeloproliferative neoplasms. Blood 123 (24): 3714-9, 2014. [PUBMED Abstract]
  12. Rumi E, Pietra D, Ferretti V, et al.: JAK2 or CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes. Blood 123 (10): 1544-51, 2014. [PUBMED Abstract]
  13. Rotunno G, Mannarelli C, Guglielmelli P, et al.: Impact of calreticulin mutations on clinical and hematological phenotype and outcome in essential thrombocythemia. Blood 123 (10): 1552-5, 2014. [PUBMED Abstract]