TARGETING JAK2 in myeoloproliferative neoplasms (MPN)
Myeloproliferative Neoplasms (MPNs) are blood cancers that occur when the body makes too many white or red blood cells, or platelets. This overproduction of blood cells in the bone marrow can create problems for blood flow and lead to various symptoms. MPNs were called Myeloproliferative Diseases until 2008 when the World Health Organization re-classified them as cancers and named them Myeloproliferative Neoplasms.
There are three main types of MPNs:
- Primary Myelofibrosis (PMF)
- Polycythemia vera (PV)
- Essential thrombocythemia (ET)
Certain leukemias, including chronic myelogenous leukemia, are also now considered Myeloproliferative Neoplasms.
WHO (in 2008) classification of PMF includes JAK2 (V617F) or MPL (W515) mutations as a key diagnostic benchmark that undeniably proves the clonal nature of the disease. Nevertheless, ongoing research has elucidated other somatic mutations as well. Mutations of CALR gene encoding calreticulin, have been found in 20% to 25% of patients with essential thrombocythemia (ET) or PMF. Similar to JAK2 and MPL mutations, somatic mutations of CALR have been implicated for the myeloproliferative phenotype.