Test Catalog

Test ID: JAKXM    
JAK2 Exon 12 and Other Non-V617F Mutation Detection, Bone Marrow

Useful For Suggests clinical disorders or settings where the test may be helpful

Second-order testing to aid in the distinction between a reactive cytosis and a myeloproliferative neoplasm, particularly when a diagnosis of polycythemia is being entertained; for use with bone marrow specimens

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

This is a second-order test that should be used when the test for the JAK2M / JAK2 V617F Mutation Detection, Bone Marrow test is negative.


See Myeloproliferative Neoplasm: A Diagnostic Approach to Bone Marrow Evaluation in Special Instructions.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

DNA sequence mutations in the Janus kinase 2 (JAK2) gene are found in the hematopoietic cells of several myeloproliferative neoplasms (MPN), most frequently polycythemia vera (close to 100%), essential thrombocythemia (approximately 50%), and primary myelofibrosis (approximately 50%). Mutations in JAK2 have been reported at much lower frequency in other MPN, chronic myelomonocytic leukemia and mixed MPN/myelodysplastic syndromes, but essentially never in chronic myelogenous leukemia (CML), reactive cytoses, or normal patients. Mutations are believed to cause constitutive activation of the JAK2 protein, which is an intracellular tyrosine kinase important for signal transduction in many hematopoietic cells. Since it is often difficult to distinguish reactive conditions from the non-CML MPN, identification of a JAK2 mutation has diagnostic value. Potential prognostic significance of JAK2 mutation detection in chronic myeloid disorders has yet to be clearly established.


The vast majority of JAK2 mutations occur as base pair 1849 in the gene, resulting in a JAK2 V617F protein change. In all cases being evaluated for JAK2 mutation status, the initial test that should be ordered is JAK2M / JAK2 V617F Mutation Detection, Bone Marrow, a sensitive assay for detection of the mutation. However, if no JAK2 V617F mutation is found, further evaluation of JAK2 may be clinically indicated. Over 50 different mutations have now been reported within exons 12 through 15 of JAK2 and essentially all of the non-V617F mutations have been identified in polycythemia vera. These mutations include point mutations and small insertions or deletions. Several of the exon 12 mutations have been shown to have biologic effects similar to those caused by the V617F mutation such that it is currently assumed other nonpolymorphic mutations have similar clinical effects. However, research in this area is ongoing.


This assay for non-V617F/alternative JAK2 mutations is designed to obtain the sequence for JAK2 exons 12 through the first 90% of exon 15, which spans the region containing all mutations reported to date.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation Provides information to assist in interpretation of the test results

The results will be reported as 1 of 2 states:

1. Negative for JAK2 mutation

2. Positive for JAK2 mutation


If the result is positive, a description of the mutation at the nucleotide level and the altered protein sequence is reported.


Positive mutation status is highly suggestive of a myeloproliferative neoplasm, but must be correlated with clinical and other laboratory features for a definitive diagnosis. Negative mutation status does not exclude the presence of a myeloproliferative or other neoplasm.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

A positive result is not specific for a particular diagnosis and clinico-pathologic correlation is necessary in all cases. A negative result does not exclude the presence of a myeloproliferative or other neoplasm.


If this test is ordered in the setting of erythrocytosis and suspicion of polycythemia vera, interpretation requires correlation with a concurrent or recent prior bone marrow evaluation.

Supportive Data

Analytical sensitivity is approximately 20% meaning there must be about 20% of the mutated DNA in the sample for reliable detection.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Ma W, Kantarjian H, Zhang X, et al: Mutation profile of JAK2 transcripts in patients with chronic myeloid neoplasias. J Mol Diagn 2009;11:49-53

2. Kilpivaara O, Levine RL: JAK2 and MPL mutations in myeloproliferative neoplasms: discovery and science. Leukemia 2008;22:1813-1817

3. Kravolics R: Genetic complexity of myeloproliferative neoplasms. Leukemia 2008;22:1841-1848

Special Instructions Library of PDFs including pertinent information and forms related to the test