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American Diagnostic Laboratory Offers Genetic Test for Calreticlin Gene Mutations

By Labmedica International staff writers
Posted on 14 Apr 2014
Image: Molecule model of calreticulin (Photo courtesy of Wikimedia Comons).
Image: Molecule model of calreticulin (Photo courtesy of Wikimedia Comons).
A new diagnostic test that detects mutations in the gene encoding for the protein calreticulin (CALR) is expected to help physicians identify patients with certain types of myeloproliferative neoplasms (MPN), which are blood cancers that have the potential to evolve into acute leukemia.

Calreticulin is a multifunctional protein that acts as a major calcium ion-binding protein in the lumen of the endoplasmic reticulum. It is also found in the nucleus, suggesting that it may have a role in transcription regulation. Calreticulin binds to antibodies in certain sera of systemic lupus and Sjogren patients which contain anti-Ro/SSA antibodies, it is highly conserved among species, and it is located in the endoplasmic and sarcoplasmic reticulum where it may bind calcium. The amino terminus of calreticulin interacts with the DNA-binding domain of the glucocorticoid receptor and prevents the receptor from binding to its specific glucocorticoid response element. Calreticulin can inhibit the binding of androgen receptor to its hormone-responsive DNA element and can inhibit androgen receptor and retinoic acid receptor transcriptional activities in vivo, as well as retinoic acid-induced neuronal differentiation. Thus, calreticulin can act as an important modulator of the regulation of gene transcription by nuclear hormone receptors.

Cancer Genetics, Inc. (Rutherford, NJ, USA), a state-of-the-art reference laboratory that is [US] Food and Drug Administration CLIA certified and CAP accredited with licensure from several states including New York State has recently begun to perform a genetic diagnostic test to detect mutations in the calreticulin (CALR) gene. These mutations can serve as important biomarkers in the diagnosis of two subtypes of patients with MPN: essential thrombocythemia (ET) and primary myelofibrosis (PMF). CALR mutations are absent in patients with JAK2 and MPL mutations, which are other well established leukemia biomarkers.

"CALR mutation analysis allows for a more comprehensive diagnosis of patients with myeloproliferative neoplasms," said Dr. Lan Wang, medical director at Cancer Genetics. "This test can help simplify the diagnosis of MPN and may be helpful in stratifying patients according to whether they should receive aggressive or conservative disease management. We see CALR mutation testing becoming one of the routine genomic tests provided to MPN patients."

Panna Sharma, CEO of Cancer Genetics said, "The CALR mutation analysis is a valuable addition to our test menu. The availability of this test positions CGI as one of the most comprehensive laboratories in the US for MPN and acute leukemia. In launching this test, we responded quickly to demand from the clinical community, demonstrating our ability to rapidly adapt in a fast-paced, evolving environment."

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