Gender and age characteristics of <I>JAK2</I> V617F mutation allelic burden and <I>CALR</I> and <I>MPL</I> driver mutations detection during primary examination of patients with suspected myeloproliferative neoplasms

Abstract

Background. Detection of a somatic mutation in the Janus kinase 2 (JAK2) gene, along with mutations in the CALR and MPL genes, is one of the main criteria for diagnosing Ph-negative myeloproliferative neoplasms (MPN). At the same time, the JAK2 V617F mutation is often associated with agedependent clonal hematopoiesis of undetermined potential (CHIP). As a rule, the indicator reflecting the number of blood cells transformed by mutation – the mutant allelic burden (MAB) of JAK2 V617F in CHIP does not exceed 1–2 %, however, there is no clear boundary between the level of this indicator separating CHIP and MPN. The previously described “JAK2 paradox”, according to which JAK2 V617F positive CHIP predominates in men, and for women this mutation is more associated with MPN, suggests a different attitude to the diagnostic value of MAB between men and women. A separate issue concerns the detection of low MAB levels in combination with other MPN driver mutations.Aim. To analyze the database of JAK2 V617F mutation allelic burden quantitative assessment results and to identify CALR and MPL genes driver mutations in patients depending on their age and gender.Materials and methods. Data from records on the age and gender of 6210 patients (3061 men and 3149 women) were analyzed, in whom the JAK2 gene V617F somatic mutation in a quantitative format and MPL and CALR genes mutations were simultaneously determined. Of these, mutations were identified in 1226 women and 826 men with symptoms of MPN. Statistical analysis was performed using Excel spreadsheets and Statistica 10 package.The results. The data obtained indicate that in women, compared to men, the frequency of the V617F mutation is higher in all age ranges. omen are also more likely to have mutations in the CALR and MPL genes. The gender and age dependence of identifying quantitative values of MAB JAK2 V617F differ significantly in the range of >1 and ˂ 1%. Also noteworthy is the fact of high detection (up to 17–27 %) of additional combined mutations in the CALR and MPL genes in patients with low MAB JAK2 V617F values.Conclusion. The data support the gender “JAK2 paradox”, which suggests differential interpretation of test results in men and women. To more clearly assess the characteristics of the diagnostic value of MAN JAK2 V617F low levels and its dependence on the gender and age of patients, controlled multicenter clinical studies using standardized diagnostic test systems are needed.

Keywords

• myeloproliferative disease
• allelic burden
• jak2 v617f