Molecular Test Detects Difficult-to-Diagnose Chronic Blood Cancer

The Janus kinase 2 gene (JAK2) occurs in many myeloproliferative neoplasms, but the molecular pathogenesis of myeloproliferative neoplasms with nonmutated JAK2 is obscure, and the diagnosis of these neoplasms remains a challenge.

A collaborating team of scientists from the University of Cambridge (UK) and the Wellcome Trust Sanger Institute (Hinxton, UK) and other institutes performed exome sequencing of samples obtained from 151 patients with myeloproliferative neoplasms. The mutation status of the gene encoding calreticulin (CALR) was assessed in an additional 1,345 hematologic cancers, 1,517 other cancers, and 550 controls. They established phylogenetic trees using hematopoietic colonies and assessed calreticulin subcellular localization using immunofluorescence and flow cytometry.

The team analyzed the results of exome sequencing of DNA from granulocytes and constitutional DNA obtained from purified T cells or buccal cells in 168 patients with myeloproliferative neoplasms. The identification of appropriate constitutional DNA samples is a challenge among patients with myeloproliferative neoplasms, since circulating T cells and buccal cells may be contaminated by neoplastic cells. On sequencing the patients' DNA, the scientists identified a new gene called CALR, the mutations of which were associated with chronic blood cancer. They also noticed a rise in platelet counts and a decline in hemoglobin levels associated with JAK2 mutation.

The authors concluded that detection of CALR mutations in peripheral blood could potentially be used as a diagnostic tool in the same way that tests for JAK2 mutations have simplified and improved the accuracy of diagnosis of patients with myeloproliferative neoplasms worldwide. Peter J. Campbell, MB, ChB, PhD, from the Sanger Institute, who co-led the research, said, “There is now a sense of completeness with these disorders , the vast majority of our patients can now have a definitive genetic diagnosis made. In the next year or two, we will see these genetic technologies increasingly used in the diagnosis of all cancers, especially blood cancers.” The study was published on December 10, 2013, in the New England Journal of Medicine.

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University of Cambridge
Wellcome Trust Sanger Institute