Is Low Positive JAK2 V617F Mutation Test Result Clinically Significant?: Multi-Institutional Study.

Abstract

Acquired somatic mutation Janus kinase 2 (JAK2) V617F is associated with various myeloproliferative neoplasms (MPN). Allele-specific real-time polymerase chain reaction has been widely adopted to detect mutation; however, the utility of low positive results is not well understood. The aim of this study is to investigate the clinical significance of low positivity of JAK2 V617F. Retrospective analysis was performed for JAK2 V617F mutation tests performed using JAK2 MutaQuant kit (Ipsogen) in molecular laboratories at 2 major academic medical centers between 2010 and 2012. Cases with low positive JAK2 V617F, defined as 0.2% to 5% mutant allele, were documented. Chart review was performed for the clinical correlation. A total of 1697 JAK2 V617F tests was performed. Forty-five cases (2.65%) yielded a low JAK2 V617F positivity (average 1.45%), the majority of which (n=26, 62%) had <1%. Eight cases had a history of MPN. The remaining cases were related to reactive conditions without a clonal disease. Our data indicate that a low positivity of JAK2 V617F can be seen in MPN as well as reactive conditions. An interpretation of JAK2 V617F status should not be performed simply following some arbitrary cutoff. Any low positivity of JAK2 V617F should be reported and a correlation with clinical information is warranted for proper interpretation.