Balkan Journal of Medical Genetics

EVALUATION OF THE JAK2V617F MUTATIONAL BURDEN IN PATIENTS WITH PHILADELPHIA CHROMOSOME NEGATIVE MYELOPROLIFERATIVE NEOPLASMS: A SINGLE-CENTER EXPERIENCE
Popova-Labachevska M1, Panovska-Stavridis I1,*, Eftimov A2, Kapedanovska Nestorovska A2, Cevreska L1, Ivanovski M1, Ridova N1, Trajkova S1, Dimovski AJ2,*
*Corresponding Author: Associate Professor Irina Panovska-Stavridis, M.D., Ph.D., University Clinic of Hematology, UKIM-Faculty of Medicine, University Cyril and Methodious,” Majka Tereza 47, Skopje, RN Macedonia. Tel/Fax: +38923111749. E-mail: ukhematologija@t.mk and/or Professor Aleksandar J. Dimovski, M.D., Ph.D., Center for Biomolecular Pharmaceutical Analyses, UKIM-Faculty of Pharmacy, University “Ss Cyril and Methodius,” Majka Tereza 47, Skopje, RN Macedonia. Tel/Fax: +38923119694. E-mail: adimovski@ff.ukim.edu.mk
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DISCUSSION

In an attempt to explain the association of the single mutation with three different clinical phenotypes, the genedosage hypothesis postulates that the ratio between the mutant type and wild JAK2 type in hematopoietic cells influences the expression of the clinical phenotype [5-7]. As patients with MPNs often present with overlapping clinical signs, symptoms and morphological findings, several studies have been conducted to test this hypothesis [5-7]. They have shown that the JAK2 mutational load is associated with specific hematological and clinical parameters in different MPN entities [9]. It has been suggested that a mutant allele burden of >50.0% is associated with older age, clinical signs and symptoms of PV, a more severe clinical course with a higher rate of thrombosis and a faster progression to myelofibrosis compared to a mutant allele burden <50.0% [9,10]. Other studies showed that the JAK2 allele burden could be used for stratification of patients into subgroups associated with different frequency of complications [9]. Although, the WHO criteria does not specify a cutoff value for the diagnosis of a specific MPN, the determination of the mutational load is becoming a potential diagnostic procedure in most molecular laboratories worldwide and, in addition, it may be useful in evaluating the response to therapy [1]. Another perspective of the evaluation of the allele burden is its utility as a follow-up tool during the treatment of JAK2V617F positive patients [9]. However, the specific utility of the JAK2V617F allele burden for measuring the MPN patients’ response to treatment is yet to be established [11]. In our group of patients, there was a statistically significant difference in the percentage of the mutant allele between ET and PMF patients (p <0.00001) and between PV and PMF patients (p <0.05), but not between PV and ET patients (p = 0.38). These findings are consistent with several previous studies that showed a significantly higher JAK2 allele burden in PV and PMF patients in contrast to ET patients [9]. Several studies have discussed the JAK2 allele burden impact on disease transformation and its utility in predicting disease transformation [9,10]. Our results showed that in the presence of a higher V617F allele burden, a diagnosis of PV and PMF should be strongly considered, because the burden of the mutated allele correlates with the MPN phenotype and a major clinical endpoint [9-11].

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