According to two studies presented at the 2013 Annual Meeting of the American Society of Hematology (ASH), mutations in the CALR gene may contribute to the development of some myeloproliferative neoplasms.
Myeloproliferative neoplasms (MPN) are a related group of blood cancers. In these disorders, the bone marrow cells that produce blood cells develop and function abnormally. The three main types of MPN are polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). In addition to developing on its own, myelofibrosis may also develop as a result of ET or PMF.
A recent advance in the understanding of these cancers is the identification of gene mutations that contribute to their growth. Mutations in the JAK2 and MPL genes are present in many people with MPN, but not all; researchers continue to search for additional gene mutations that drive these cancers.
In one of the studies presented at ASH (1), researchers evaluated tumor tissue from six patients with MPNs. Recurring mutations were identified in the CALR gene, prompting the researchers to screen more than 1,000 additional patients for these gene mutations. CALR mutations were detected in a majority of patients with ET or PMF that did not have JAK2 or MPL mutations. CALR mutations were not found in patients with certain leukemias or related blood disorders.
A separate study also identified CALR mutations in a majority of MPN patients without JAK2 or MPL mutations (2). Ninety-seven percent of patients screened had a mutation in of these three genes (JAK2, MPL, or CALR). CALR mutations were not found in patients with lymphoid cancers, solid tumors, or healthy controls.
These two studies also suggested that disease characteristics (such as blood cell counts) among people with MPN may vary depending on what type of gene mutation is present.
The identification of new gene mutations may facilitate the diagnosis of MPNs, and could also suggest new ways to treat these cancers.
- Thorsten K et al. Frequent Mutations in the Calreticulin Gene CALR in Myeloproliferative Neoplasms. Presented at the 55th ASH Annual Meeting and Exposition. New Orleans, LA. December 7-10, 2013. Abstract LBA-1.
 Nangalia J et al. The Genomic Landscape of Myeloproliferative Neoplasms: Somatic CALR Mutations in the Majority of JAK2-Wildtype Patients. Presented at the 55th ASH Annual Meeting and Exposition. New Orleans, LA. December 7-10, 2013. Abstract LBA-2.