(HealthDay News) – Many patients with myeloproliferative neoplasms without mutations in the Janus kinase 2 gene (JAK2) or in the thrombopoietin receptor gene (MPL) have mutations in the CALR gene encoding calreticulin, according to two studies published online Dec. 10 in the New England Journal of Medicine. The research was published to coincide with presentation at the annual meeting of the American Society of Hematology, held from Dec. 7–10 in New Orleans.

Thorsten Klampfl, PhD, from the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences in Vienna, and colleagues performed whole-exome sequencing to identify somatic mutations in six patients with primary myelofibrosis without mutations in JAK2 or MPL. The researchers identified somatic insertions or deletions in exon 9 of CALR in all patients. Among patients with essential thrombocythemia and primary myelofibrosis, CALR mutations were mutually exclusive with JAK2 and MPL mutations. CALR mutations were seen in 67% and 88%, respectively, of those with essential thrombocythemia and primary myelofibrosis, with non-mutated JAK2 or MPL.

Jyoti Nangalia, M.B.Chir., from the Cambridge Institute for Medical Research in the United Kingdom, and colleagues performed exome-sequencing of samples from 151 patients with myeloproliferative neoplasms. The researchers identified 1,498 mutations, with somatic CALR mutations in 70–84% of myeloproliferative neoplasms with non-mutated JAK2. The mutations were located in exon 9 and generated a +1 base-pair frameshift.

“Somatic mutations in the endoplasmic reticulum chaperone CALR were found in a majority of patients with myeloproliferative neoplasms with non-mutated JAK2,” Nangalia and colleagues write.

Several authors from the Klampfl study reported holding pending patent applications regarding the use of calreticulin gene mutations for the diagnosis of diseases and targeting for therapy for myeloproliferative neoplasms.

Abstract – Klampfl
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Abstract – Nangalia
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