Hematologic Diseases

Detects CALR mutations, which are found in a subset of myeloproliferative neoplasms (MPN). DNA sequence of exon 9 of the CALR gene is determined using amplicon-based, next-generation sequencing (NGS) technology.

disease state indication(s)
Myeloproliferative neoplasms (MPN), essential thrombocythemia (ET), primary myelofibrosis (PMF)

clinical use
CALR mutations are found in 60-90% of primary myelofibrosis and 50-70% of essential thrombocythemia that are negative for JAK2 and MPL mutations, and are included as one of the major diagnostic criteria for primary myelofibrosis and essential thrombocythemia the World Health Organization (WHO) classification of hematopoietic neoplasms. CALR mutations are associated with a more favorable prognosis and lower risk of thrombosis in patients with primary myelofibrosis and essential thrombocythemia compared to JAK2 mutations [1-3]. The favorable prognostic effect of CALR mutations in primary myelofibrosis, however, appears restricted to type 1 (52-bp deletion, p.L367fs*46) or type 1-like variants [4].

1. Klampfl T, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med 2013;369:2379-2390.
2. Tefferi A, et al. CALR and ASXL1 mutations-based molecular prognostication in primary myelofibrosis: an international study of 570 patients. Leukemia 2014;28;1494-1500.
3. Finazzi MC, et al. CALR mutation, MPL mutation and triple negativity identify patients with lowest vascular risk in primary myelofibrosis. Leukemia 2015;29:1209-1210.
4. Tefferi A, et al. The prognostic advantage of calreticulin mutations in myelofibrosis might be confied to type 1 or type 1-like CALR variants. Blood 2014;124:2465-2466.

methodology/product platform
Amplicon-based, next-generation sequencing (NGS)

specimen type and requirements
Peripheral blood: 2-3 mL in EDTA (purple-top) tube.
Bone marrow: 2-3 mL in EDTA (purple-top) tube.
Note: Use refrigerated cold pack for transport. Make sure cold pack is not in direct contact with specimen.

turnaround time
Global (TC & PC): 10-12 days

cpt code(s)
81219 (x1)

medicare moldx cpt code
81450 (x1)

regulatory classification
Laboratory developed test (LDT)

ordering option
Global (TC & PC)