Sorted By Test Name - Mayo Medical Laboratories

JAK2M
31155
Useful For: Aiding in the distinction between a reactive cytosis and a chronic myeloproliferative
disorder
Interpretation: The results will be reported as 1 of the 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 must 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.
Reference Values:
An interpretive report will be provided.
Clinical References: 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;352:1779-1790 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
JAK2 V617F Mutation Detection, Bone Marrow
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. Recently, a point mutation in JAK2
(V617F) was identified 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.
Useful For: Aiding in the distinction between a reactive cytosis and a chronic myeloproliferative
disorder
Interpretation: The results will be reported as 1 of the 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 must 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.
Reference Values:
An interpretive report will be provided.
Clinical References: 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,
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