Clinical and molecular genetic characterization of myelofibrosis

The myeloproliferative neoplasms include polycythemia vera, essential thrombocythemia, and myelofibrosis. Of these, myelofibrosis often has the most aggressive course. There is, however, often significant clinical heterogeneity among patients with myelofibrosis. We seek to summarize recent clinical and biological findings in myelofibrosis as well as review the spectrum of clinically relevant mutation in myelofibrosis and their implications.

The mutational spectrum in myelofibrosis includes driver mutations in genes such as JAK2, calreticulin, and myeloproliferative leukemia virus oncogene. In addition, recurrent mutations in epigenetic modifiers such as ASXL1 and TET2 have also been described. Importantly, several studies have indicated that specific mutations, as well as the number of mutations, that a patient bears may have important clinical consequences. The presence or absence of certain mutations may help to determine a patient's risk for thrombosis, leukemic transformation, and survival.

Myelofibrosis often has variable outcomes among patients. Prognostic systems based on clinical observations have been developed in an attempt to predict risks of disease progression and transformation. The discovery of recurrent genomic alterations in myelofibrosis, and the observation that many of these alterations may help predict clinical outcomes, has heralded a new era in the biologic understanding and clinical approach to myelofibrosis.