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)
  • Infrequently (3-5%) in myelodysplastic syndrome (MDS) & CMML
  • JAK2 V617F mutation (auto-inhibitory domain) activates the kinase

 Clinical Utility of Direct Quantitative Test for the V617F JAK2 Allele Burden:

  • To correlate with clinical splenomegaly, pruritus, leukocytosis 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:

Allele-specific polymerase chain reaction.

Sensitivity:
This assay is quantitative for the V617F JAK2 mutation and is capable of detecting V617F at 0.1% 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: 100ng at minimum of 100ng/µL (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS)
  •  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 overnight label provided.
  • Contact Client Services for shipping kit and instructions at (855) 535-1522.

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.

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.

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