Calreticulin mutations help diagnose occult myeloproliferative neoplasms in patients with splanchnic vein thrombosis

Myeloproliferative neoplasms (Fildadelfia chromosome-negative) are the most common cause of splanchnic vein thrombosis, but they are often masked. A study led by IDIBAPS has found that screening for mutations in the gene encoding calreticulin (CALR) increases the number of diagnoses of this type of cancer and may reduce the need for additional studies, such as bone marrow biopsy, in some patients. This is the first study to evaluate the frequency of these mutations in a large number of patients.

In the study, published in the Journal of Hepatology, have participated researchers working at the following groups at IDIBAPS: Regulation of liver microcirculation in cirrhosis and hepatic vascular diseases, headed by Dr. Juan Carlos García-Pagán, Hematological oncology, led by Dr. Francisco Cervantes and Physiopathology and molecular bases in hematology, headed by Dr. Dolors Colomer. Dr. Fanny Turón, working in the group led by Dr. García-Pagán, is the first author of the article.

The term "Splanchnic Vein Thrombosis" includes the diseases known as Budd-Chiari syndrome, or hepatic vein thrombosis, and portal vein thrombosis (PVT). The myeloproliferative neoplasms (MPN) are the leading cause of this type of thrombosis and are detected in 35% of patients with PVT and in 50% of those with the Budd-Chiari syndrome. Although they are quite difficult to diagnose, as they are often masked, the discovery of mutations in the JAK2 gene has simplified the diagnosis, as it occurs in a great majority of patients with MPN. Recently, various studies have also reported mutations in the gene encoding calreticulin (CALR), which occur in a high percentage of patients without the JAK2 mutation.

With this information, researchers conducted a retrospective study with samples from 209 patients with splanchnic vein thrombosis to search for mutations in JAK2 and CALR. 35% of the patients analyzed had a myeloproliferative neoplasm and of those, 82.4% had a mutation in JAK2 and nearly 6% in the CALR gene. The results confirmed that the two mutations were mutually exclusive, which means that, if one occurs, the other does not.

Regarding the results, mutations in JAK2 should be studied first because of their higher frecuency in patients with splachnic vein thrombosis. If it is not found, there should be investigated if the CALR gene is mutated. Thus, the diagnosis of myeloproliferative neoplasms will be improved in patients with this type of thrombosis and there will be a reduced need for more invasive procedures.

Article reference:

Role of calreticulin mutations in the etiological diagnosis of splanchnic vein thrombosis.

Turon F, Cervantes F, Colomer D, Baiges A, Hernández-Gea V, Garcia-Pagán JC. J Hepatol. 2014 Aug 27. pii: S0168-8278(14)00619-9. doi: 10.1016/j.jhep.2014.08.032. [Epub ahead of print]