Calreticulin (CALR) Mutation Analysis
UFHPL Epic order code: LAB5435
Specimen: Whole blood, bone marrow or cell pellet
Volume: 3 to 5 mL whole blood or 1 to 2 mL bone marrow
Container: Lavender-top (EDTA) tube or green-top (sodium heparin) tube
Collection: Ship specimen at room temperature. Specimen should arrive in the laboratory within 48 hours of collection. If specimen is to be stored prior to shipment, store at 2°C to 8°C. Indicate date and time of collection on the test request form.
Storage Instructions: Refrigerate. Stable for 72 hours at room temperature or refrigerated.
The calcium-binding endoplasmic reticulin chaperone protein, calreticulin (CALR), is somatically mutated in approximately 70% of patients with JAK2-negative essential thrombocythemia (ET) and 60% to 88% of patients with JAK2-negative primary myelofibrosis (PMF). Only a minority of patients (approximately 8%) with myelodysplasia have mutations in CALR gene. CALR mutations are rarely detected in patients with de novo acute myeloid leukemia, chronic myelogenous leukemia, lymphoid leukemia, or solid tumors. CALR mutations are not detected in polycythemia and generally appear to be mutually exclusive with JAK2 mutations and MPL mutations.
The majority of mutational changes involve a variety of insertion or deletion mutations in exon 9 of the calreticulin gene: approximately 53% of all CALR mutations are a 52 bp deletion (type-1) while the second most prevalent mutation (approximately 32%) contains a 5 bp insertion (type-2). Other mutations (non-type 1 or type 2) are seen in a small minority of cases. CALR mutations in PMF tend to be associated with a favorable prognosis compared to JAK2V617F mutations, whereas primary myelofibrosis negative for CALR, JAK2V617F and MPL mutations (so-called triple negative) is associated with a poor prognosis and shorter survival.
The detection of a CALR gene mutation aids in the specific diagnosis of a myeloproliferative neoplasm, and helps distinguish this clonal disease from a benign reactive process.
Polymerase chain reaction (PCR); capillary electrophoresis
5 - 7 days