JAK2 V617F Mutation Analysis – a highly specific and sensitive assay to aid in the diagnosis of bcr/abl-negative myeloproliferative disorders – is now available at AmeriPath. Click here to read the press release.

For more information – JAK2 V617F Mutation Analysis (PDF).

Overview | Clinical Utility | Specimen Requirements | Specimen Storage and Transport | Methodology | Turnaround Time | Result

Overview

The myeloproliferative disorders (MPDs) are clonal stem cell diseases distinguished by the proliferation of mature granulocytes, red blood cells, and/or platelets. Several recent studies have found a close association between the JAK2 (Janus kinase 2) V617F mutation and the classic bcr/abl-negative MPDs; polycythemia vera (PV), essential thrombocythemia (ET), and idiopathic myelofibrosis (IM). (This same mutation has been found to occur much less frequently in atypical MPDs and myelodysplastic syndromes.) JAK2 is a cytoplasmic protein-tyrosine kinase; the V61F mutation results in constitutive JAK2 activity and enhanced JAK2-signal transducers and activators of transcription (STAT) signaling. Studies have demonstrated this mutation in 65-97 percent of PV, 23-57 percent of ET, and 35-57 percent of IM patients. Additionally, some studies have described a mutant allele dose effect on the phenotype of PV related to erythrocytosis and other clinical or laboratory features. The description of the JAK2 V617F mutation may be of benefit in the development of a molecular-based classification, refined diagnostic criteria, and therapeutic targets for the classic bcr/abl-negative MPDs.

Clinical Utility

• Aid in or confirm the diagnosis of PV, ET, or IM
• Help distinguish PV from secondary erythrocytosis
• Help distinguish ET from reactive thrombocytosis
• May help distinguish IM from MDS or atypical MPDs
• Complementary to (not a substitute for) bone marrow histology and cytogenetics
• May preclude the need for other diagnostic testing
• May be a target for future MPD therapy

Specimen Requirements

• Preferred – 3-5 mL whole blood in purple-top (EDTA) tube
• Alternate – 1-2 mL bone marrow in purple-top (EDTA) tube
• Alternate – 3-5 mL whole blood in yellow-top (ACD) or green-top (sodium heparin) tube

Specimen Storage and Transport

• Store at room temperature, refrigerate if stored overnight, and do not freeze.
• Transport with refrigerated cold pack in AmeriPath Oncology Diagnostics’ specimen transport kit.
• The specimen should arrive at the laboratory as soon as possible after collection; indicate the date and time of collection on the hematopathology requisition form.

Methodology

Target gene amplification using real-time polymerase chain reaction with differentially labeled, allele-specific primers that allow the identification and quantitation of JAK2 wild-type and V617F mutant alleles

Turnaround Time

• Three days from specimen receipt to reporting
• Upon release, reports are immediately available via fax, remote printing, or online Physician WebPortal.

Result

• Positive for JAK2 V617F mutation
• Negative for JAK2 V617F mutation

 

References

• Kralovics, R., F. Passamonti, A. Buser, S-S Teo, R. Tiedt, J. Passweg, A. Tichelli, M. Cazzola, and R. Skoda. 2005. A gain-of-function mutation of JAK2 in myeloproliferative disorders. New England Journal of Medicine 352(17):1779-90.
• Tefferi, A. and T. Barbui. 2005. Bcr/abl-negative, classic myeloproliferative disorders: Diagnosis and treatment. Mayo Clinic Proceedings 80(9):1220-32.
• Tefferi, Al, and G. Gilliland. 2005. The JAK2 V617F tyrosine kinase mutation in myeloproliferative disorders: Status report and immediate implications for disease classification and diagnosis. Mayo Clinic Proceedings 80(7):947-58.
• Tefferi, A., T. Lasho, S. Schwager, J. Strand, M. Elliott, R. Mesa, C. Li, M. Wadleigh, S. Lee, and G. Gilliland. 2005. The clinical phenotype of wild-type, heterozygous, and homozygous JAK2 V617F in polycythemia vera. Cancer 106(3):631-635.