Background:

Chronic myeloproliferative diseases (CMPDs) are clonal hematopoietic stem cell disorders characterized by proliferation of one or more myeloid cell lineages in the bone marrow and increased numbers of mature and immature cells in the peripheral blood.  CMPDs include polycythemia vera (PV), essential thrombocythemia (ET), idiopathic myelofibrosis (IMF), and chronic myeloid leukemia (CML).  Most patients with myeloproliferative disorders carry a V617F JAK2 mutation: 74 - 97% of patients with polycythemia vera (PV); 33 - 57% of patients with essential thrombocythemia (ET); 35 - 50% of patients with myelofibrosis (IMF); and also present infrequently (3-5%) in myelodysplastic syndrome (MDS) & CMML.

In conjunction with a histopathologic evaluation, the World Health Organization diagnostic criteria for polycythemia vera include a test for the JAK2 V617F mutation in exon 14.  Alternatively, the presence of a JAK2 exon 12 mutation also meets the WHO criterion for molecular evidence of clonality in cases negative for JAK2 V617F.  Typically, JAK2 exon 12 mutation for PV is indicated when the V617F mutation has been ruled out.

Clinical Utility of Direct Quantitative Test for the V617F or Exon 12 Allele Burden:

  • To correlate with clinical splenomegaly, pruritus, leukocytosi or myelofibrosis
  • To monitor disease burden post-treatment or as a marker for therapeutic intervention
  • To identify prognostically relevant clonal proliferation
  • JAK2 targeted therapies may soon be available

Methodology:

JAK2 exon 12 mutation is detected by cold-PCR followed by High Resolution Melt Curve analysis. Postive mutations are confirmed by Sanger sequencing.

Sensitivity:
Approximately 20% mutant allele abundance in a background of wild-type gene targets.
 
Specificity:
A clinical correlation is imperative for the interpretation of a result of this test

Specimen Requirements:

  • 5-10 mL of blood or bone marrow — yellow (ACD) or purple (EDTA) tube. 
  • DNA: 200ng at a minimum of 25ng/µL  (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS)
  • Contact Client Services for shipping kit and instructions at (855) 535-1522. 
  • If sample cannot arrive at laboratory within 24 hours of draw, refrigerate until sample can be transported.
A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information.

Test Performed (Days):

Weekly

Turn Around Time:

7-10 days

Shipment Sensitivity Requirements:

  • Keep specimen cold during transit, but do not ship on dry ice.
  • Please use the cold pack provided in the KDL shipping kit.
  • Ship the specimen overnight express, using the FedEx priority label provided.

References:

  1. Baxter, EJ.  Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders.  Lancet 2005; 365: 1054 – 1061.
  2. Kralovics, R.  A gain-of-function mutation of JAK2 in Myeloproliferative disorders. N Engl J Med 2005; 352: 1779 – 1790.
  3. Jones, A. et al.  Widespread occurrence of the JAK2 V617F Mutation in Chronic Myeloproliferative Disorders.  Blood 2005; 106: 2162 - 2168.
  4. Tafferi, A. Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH, and IKZF1. Leukemia 2010; 24: 1128-1138.
  5. Scott, LM. et al. JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. New Engl J Med 2007; 356:459-468.
  6. Pardanani A. et al. Prevalence and clinicopathologic correlates of JAK2 exon 12 mutations in JAK2 V617F-negative polycythemia vera.  Leukemia 2007; 21:1960-1963.

Additional Info:




The Knight Cancer Institute at Oregon Health & Science University is a pioneer in the field of precision cancer medicine. The institute's director, Brian Druker, M.D., helped prove it was possible to shut down just the cells that enable cancer to grow. This breakthrough has made once-fatal forms of the disease manageable and transformed how cancer is treated. The OHSU Knight Cancer Institute is the only National Cancer Institute-designated Cancer Center between Sacramento and Seattle – an honor earned only by the nation's top cancer centers. It is headquarters for one of the National Cancer Institute's largest research collaboratives, SWOG, in addition to offering the latest treatments and technologies as well as hundreds of research studies and clinical trials.

Learn More