Blood Res.  2013 Jun;48(2):128-132. 10.5045/br.2013.48.2.128.

The allele burden of JAK2 V617F can aid in differential diagnosis of Philadelphia Chromosome-Negative Myeloproliferative Neoplasm

• Park SH
• Chi HS
• Cho YU
• Jang S
• Park CJ

• KMID: 2172911
• DOI: http://doi.org/10.5045/br.2013.48.2.128

Abstract

BACKGROUND
We aimed to evaluate the feasibility of using the allele burden of Janus kinase 2 (JAK2) V617F as a criterion for discriminating 3 subtypes of Philadelphia chromosome-negative myeloproliferative neoplasm (Ph-MPN): polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF).
METHODS
We collected 70 peripheral blood (PB) and 81 bone marrow (BM) samples from patients diagnosed with Ph-MPN. Real-time quantitative PCR (RQ-PCR) and Amplification Refractory Mutation System (ARMS) assays were performed for each sample. We compared the allele burden of JAK2 V617F for each subtype of Ph-MPN and determined the concordance rates of the results between the 2 tests.
RESULTS
The JAK2 V617F allele burden differed significantly among the 3 disease categories in both PB (P=0.045) and BM (P=0.011) samples. Subsequent subgroup analysis revealed that the median allele burden of JAK2 V617F for ET (21.71% for PB and 24.95% for BM) was significantly lower than that for PV (56.88% for PB, P=0.047; 72.66% for BM, P=0.003) and PMF (56.16% for PB, P=0.050; 59.04% for BM, P=0.049). Concordance rate between the RQ-PCR and ARMS data was 90.7%. Of the 14 discrepant cases, 12 were RQ-PCR(+)/ARMS(-) and 2 were RQ-PCR(-)/ARMS(+).
CONCLUSION
The allele burden of JAK2 V617F was significantly lower for ET than that for PV or PMF in both PB and BM samples. The JAK2 V617F allele burden is a diagnostic tool for differentiating PV or PMF from ET.

Keyword

Allele; Discrimination; Janus Kinase 2; Mutation; Myeloproliferative disorders; Real-time polymerase chain reaction

MeSH Terms

Alleles
Arm
Bone Marrow
Diagnosis, Differential
Discrimination (Psychology)
Humans
Janus Kinase 2
Myeloproliferative Disorders
Philadelphia
Polycythemia Vera
Polymerase Chain Reaction
Primary Myelofibrosis
Real-Time Polymerase Chain Reaction
Thrombocythemia, Essential
Janus Kinase 2

Figure

• 

  Fig. 1 Comparison of the allele burden of the JAK2 V617F mutation among the subtypes of Philadelphia-negative myeloproliferative neoplasm. The median allele burden of JAK2 V617F for ET (21.71% for PB and 24.95% for BM) was significantly lower than that for PV (56.88% for PB, P=0.047; 72.66% for BM, P=0.003) and PMF (56.16% for PB, P=0.050; 59.04% for BM, P=0.049).

Reference

1. Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005; 365:1054–1061. PMID: 15781101.

2. James C, Ugo V, Le Couédic JP, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005; 434:1144–1148. PMID: 15793561.

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. PMID: 15858187.

4. Levine RL, Wadleigh M, Cools J, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. 2005; 7:387–397. PMID: 15837627.

5. Tefferi A, Thiele J, Orazi A, et al. Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel. Blood. 2007; 110:1092–1097. PMID: 17488875.

6. Passamonti F, Rumi E, Pietra D, et al. Relation between JAK2(V617F) mutation status, granulocyte activation, and constitutive mobilization of CD34+ cells into peripheral blood in myeloproliferative disorders. Blood. 2006; 107:3676–3682. PMID: 16373657.

7. Tefferi A, Strand JJ, Lasho TL, et al. Bone marrow JAK2V617F allele burden and clinical correlates in polycythemia vera. Leukemia. 2007; 21:2074–2075. PMID: 17476276.

8. Kittur J, Knudson RA, Lasho TL, et al. Clinical correlates of JAK2V617F allele burden in essential thrombocythemia. Cancer. 2007; 109:2279–2284. PMID: 17440984.

9. Hussein K, Bock O, Theophile K, et al. JAK2(V617F) allele burden discriminates essential thrombocythemia from a subset of prefibrotic-stage primary myelofibrosis. Exp Hematol. 2009; 37:1186–1193.e7. PMID: 19616600.

10. Buhr T, Büsche G, Choritz H, Länger F, Kreipe H. Evolution of myelofibrosis in chronic idiopathic myelofibrosis as evidenced in sequential bone marrow biopsy specimens. Am J Clin Pathol. 2003; 119:152–158. PMID: 12520711.

11. Larsen TS, Pallisgaard N, Moller MB, Hasselbalch HC. The JAK2V617F allele burden in essential thrombocythemia, polycythemia vera and primary myelofibrosis-impact on disease phenotype. Eur J Haematol. 2007; 79:508–515. PMID: 17961178.

12. Ha JS, Kim YK, Jung SI, Jung HR, Chung IS. Correlations between Janus kinase 2 V617F allele burdens and clinicohematologic parameters in myeloproliferative neoplasms. Ann Lab Med. 2012; 32:385–391. PMID: 23130336.