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Unit Code 83872:
JAK2 V617F Mutation Detection

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Useful For

Aiding in the distinction between a reactive cytosis and a chronic

myeloproliferative disorder

Clinical Information

The Janus kinase 2 gene (JAK2) codes for a tyrosine kinase (JAK2)

that is associated with the cytoplasmic portion of a variety of

transmembrane cytokine and growth factor receptors important

for signal transduction in hematopoietic cells. Receptor binding by

extracellular ligand causes receptor multimerization and brings

JAK2 proteins together to allow activation by transphosphorylation.

Activated JAK2 then phosphorylates the cytoplasmic portion of the

receptor creating a docking site for the latent transcription factor,

STAT5, which is also phosphorylated by JAK2. Phosphorylated

STAT5 then forms dimers that translocate into the nucleus and

initiate transcription of genes ultimately responsible for cell

growth and differentiation.

 

A point mutation in JAK2 (V617F) was identified in exon 14 and was

found to be present  in the hematopoietic cells of several chronic

myeloproliferative disorders (CMPDs), most frequently polycythemia

vera (65%-97%), essential thrombocythemia (25%-55%), and

chronic idiopathic myelofibrosis (35%-57%).(1-3) The mutation

has been reported at much lower frequency in some other CMPDs,

chronic myelomonocytic leukemia and myelodysplastic syndromes.(4)

It has not been reported in chronic myelogenous leukemia (CML),

normal patients, or reactive cytoses.(1-4) This mutation causes

constitutive activation of JAK2 and is thought to play a key role in

the neoplastic phenotype. Since it is often difficult to distinguish

reactive conditions from the non-CML CMPDs, identification of the

JAK2 mutation has diagnostic value. Potential prognostic significance

of JAK2 mutation detection in chronic myeloid disorders has yet to

be clearly established.

Reference Values

An interpretive report will be provided.

Interpretation

The results will be reported as 1 of 3 states:

-Negative for JAK2 V617F mutation.

-Below the laboratory cutoff for JAK2 V617F mutation positivity.

-Positive for JAK2 V617F mutation.

 

Positive mutation status is highly suggestive of a myeloid neoplasm,

but needs to be correlated with clinical and other laboratory features

for definitive diagnosis. Negative mutation status does not exclude

the presence of a chronic myeloproliferative disorder or other

neoplasm. Results below the laboratory cutoff for positivity are of

unclear clinical significance at this time.

Cautions

A positive result is not specific for a particular diagnosis and

clinicopathologic correlation is necessary in all cases.

 

A negative result does not exclude the presence of a chronic

myeloproliferative disorder or other neoplastic process.

Special Instructions and Forms

• MayoConnect Additional Test Information 

Clinical Reference

1.   Baxter EJ, Scott LM, Campbell PJ, et al:  Acquired mutation of

      the tyrosine kinase JAK2 in human myeloproliferative disorders.

      Lancet 2005 March 16;365(9464):1054-1061

 

2.   James C, Ugo V, Le Couedic JP, et al:  A unique clonal JAK2

      mutation leading to constitutive signaling causes polycythaemia

      vera. Nature 2005 April 28;434(7037):1144-1148

 

3.   Kralovics R, Passamonti F, Buser AS, et al:  A gain-of-function

      mutation of JAK2 in myeloproliferative disorders. N Engl J Med

      2005 April 28;352(17):1779-1790

 

4.   Steensma DP, Dewald GW, Lasho TL, et al:  The JAK2 V617F

      activating tyrosine kinase mutation is an infrequent event in

      both "atypical" myeloproliferative disorders and the

      myelodysplastic syndrome. Blood 2005;106:1207-1209

Key