JAK-2 Mutation

Why is this test performed?

Myeloproliferative neoplasms are clonal hematopoeitic stem cell malignancies characterized by independency or hypersensitivity of hematopoeitic progenitors to numerous cytokines. The myeloproliferative disorders are a heterogenous group of diseases characterized by excessive production of blood cells by hematopoietic precursors. In addition to thrombotic and hemorrhagic complications, leukemic transformation can occur. Classic myeloproliferative neoplasms encompass four related entities: chronic myelogenous leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis. Activating point mutation in the Januse Kinase 2 (JAK-2) gene was identified in 95% of cases of polycythemia vera and in about 50% of cases of essential thrombocythemia and idiopathic myelofibrosis. It is also frequently present (3-5%) in myelodysplastic syndrome (MDS) and CMML.

What is the JAK-2 mutation?

The V617F  mutation is 1849 G>T, in exon 14 of the gene, resulting in substitution of phenylalanine for valine (V617F) in the JAK-2 protein. This point mutation at amino acid residue 617 is a gain-of-function mutation that causes constitutive activation of the JAK-2 tyrosine kinase. The mutant has enhanced kinase activity and when overexpressed together with the erythropoietin receptor in cells, it causes increase in erthropoietin-induced cell signaling. The JAK-2 V617F  mutation may explain the hypersensitivity of PV progenitor cells to growth factors and cytokines.

What is the clinical significance?

  • Diagnostic work-up of BRC/ABL negative chronic myeloproliferative neoplasms
  • Meets WHO criteria for identification of a clonal marker

How does this test work?

Ipsogen’s JAK-2 MutaScreen assay is a kit based allelic discrimination assay that identifies presence of the JAK-2 V617F activating mutation allele and the wild type JAK-2 allele in genomic DNA extracted from human white blood cells. The method consists of real time dection of flourescent signals during and/or subsequent to PCR cycling. Allelic discrimination is achieved through the use of flourescently labeled probes for wild type and mutant JAK-2 alleles. A reference sample that sets up a threshold to separate positive from negative signals is included in this assay system.

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