Janus Kinase 2 Gene Mutation Assay and MPN Targeted Profile – pro
JAK2 tyrosine kinase and MPL mutation testing may be considered MEDICALLY NECESSARY in the diagnosis of patients presenting with clinical, laboratory,or pathological findings suggesting classic forms of myeloproliferative neoplasms (MPN), that is, polycythemia vera (PV), essential thrombocythemia (ET), or primary myelofibrosis (PMF).
With a negative BCR/ABL, Jak2 test is reasonable and medically necessary.
AK2 V617F is a name for a mutation a specific location in the JAK2 gene and is the primary genetic test for JAK2 mutations that are implicated in causing Myeloproliferative disorders (MPD). It is currently thought that this mutation is not the cause but a promoter of MPD.
Of the three MPD disorders, Polycithemia Vera (PD), Essential Thrombocytosis (ET) and Myelofibrosis (MF), this test is most useful for the latter two, because PD can be easily diagnosed with the Red Cell Mass test, but the ET and MF do not have a single definitive test. Therapeutically, Jakafi (ruxolitinib) is a drug directed against the JAK2 mutation. Whereas, both Jak2 positive and negative patients respond to Jakafi, response rates are higher with a positive Jak2 test.
Before Jak2 testing is performed, BCR/ABL analysis should be performed, especially in the cases in which leukocytosis is prominent. Positive testing will diagnose CML and make Jak2 analysis unnecessary. Current evidence does not support tailoring therapy to quantitative results of Jak2 testing. McKeeson Interqual Clinical Evidence on Jak2V617F Myelopropliferative Disorders recommends this test for diagnosed PV, ET and MF but says that there is limited evidence to support testing for suspected MP neoplasms, other suspected myeloid disorders for childhood ALL.
MPN Targeted Profile (81270/81450) is a newer and less established test. It remains unproven, especially in as much as it adds to teh Jal 2 tests and should not be considered medically necessary at this time.
| 1. Verstovsek S, Mesa RA, Gotlib JR, et al. Results of COMFORT-I, a randomized double-blind phase III trial of JAK 1/2 inhibitor INCB18424 (424) versus placebo (PB) for patients with myelofibrosis (MF). J Clin Oncol. ASCO Meeting Abstracts. 2011;29:6500.Harrison CN, Kiladjian J, Al-Ali HK, et al. Results of a randomized study of the JAK inhibitor ruxolitinib (INC424) versus best available therapy (BAT) in primary myelofibrosis (PMF), post-polycythemia vera-myelofibrosis (PPV-MF) or post-essential thrombocythemia-myelofibrosis (PET-MF). J Clin Oncol. ASCO Meeting Abstracts. 2011;29:LBA6501. 2.Gong JZ1, Cook JR, Greiner TC, Hedvat C, Hill CE, Lim MS, Longtine JA, Sabath D, Wang YL; Association for Molecular Pathology. Laboratory practice guidelines for detecting and reporting JAK2 and MPL mutations in myeloproliferative neoplasms: a report of the Association for Molecular Pathology. J Mol Diagn. 2013 Nov;15(6):733 3. J. V. Melo, T. P. Hughes, and J. F. Apperley. Chronic Myeloid Leukemia. Hematology, January 1, 2003; 2003(1): 132 – 152. 4. .Jean-Jacques Kiladjian The spectrum of JAK2-positive myeloproliferative neoplasms ASH Education Book December 8, 2012 vol. 2012 no. 1 561-566 5.Elisa Rumi and Mario Cazzola, Diagnosis, risk stratification, and response evaluation in classical myeloproliferative neoplasms. Blood. 2017 Feb 9; 129(6): 680692. |