Myeloproliferative neoplasm risk factors

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Mohamad Alkateb, MBBCh [2] Shyam Patel [3]

Overview

There are four major categories of risk factors for myeloproliferative neoplasm. Genetic mutational events comprise the most common risk factor. Other risk factors include advanced age, prior cytotoxic chemotherapy, and autoimmune disease.

Risk factors

  • Mutations: Genetic mutations are the most important risk factors for development of myeloproliferative neoplasm. Mutations in JAK2, CALR, and MPL are the most common risk factors for myeloproliferative neoplasms and are causative mutations in the disease. There are multiple other genetic mutations associated with myeloproliferative neoplasms (please see Causes section).
  • Advanced age: Age is a major risk factor for the development of myeloproliferative neoplasm. Aging is associated with the acquisition of mutations in cells, and these mutations can lead to the development of hematologic malignancies.
  • Prior cytotoxic therapy: Treatment-related myeloproliferative neoplasms is emerging as an important clinical entity to recognize [1] Patients who receive chemotherapy for other conditions are at risk for developing myeloproliferative neoplasms after many years. The reason for treatment related myeloproliferation is that cytotoxic agents induce DNA damage, which results in increased oncogenic potential within cells. Alkylating agents and topoisomerase II inhibitors are the most commonly implicated agents. Hydroxyurea is also implicated in the development of myeloproliferative neoplasms.
  • Autoimmunity: A prior history of autoimmune disease is associated with a risk for developing myeloproliferative neoplasms.[2] The etiology for the link between autoimmunity and myeloproliferative neoplasm is thought to be antigenic stimulation which results in immune cell activation and aberrant proliferation. There is specifically an increased risk of myeloproliferative neoplasm is patients with:

References

  1. Björkholm M, Derolf AR, Hultcrantz M, Kristinsson SY, Ekstrand C, Goldin LR; et al. (2011). "Treatment-related risk factors for transformation to acute myeloid leukemia and myelodysplastic syndromes in myeloproliferative neoplasms". J Clin Oncol. 29 (17): 2410–5. doi:10.1200/JCO.2011.34.7542. PMC 3107755. PMID 21537037.
  2. Kristinsson SY, Landgren O, Samuelsson J, Björkholm M, Goldin LR (2010). "Autoimmunity and the risk of myeloproliferative neoplasms". Haematologica. 95 (7): 1216–20. doi:10.3324/haematol.2009.020412. PMC 2895049. PMID 20053870.

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