The relevance of a low JAK2 V617F allele burden in clinical practice: a monocentric study

// Margherita Perricone 1, * , Nicola Polverelli 1, * , Giovanni Martinelli 1 , Lucia Catani 1 , Emanuela Ottaviani 1 , Elisa Zuffa 1 , Eugenia Franchini 1 , Arbana Dizdari 1 , Dorian Forte 1 , Elena Sabattini 2 , Michele Cavo 1 , Nicola Vianelli 1 , Francesca Palandri 1 1 Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology ‘L. and A. Seragnoli’, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy 2 Haematopathology Unit, Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy * These authors contributed equally to this work Correspondence to: Francesca Palandri, email: francesca.palandri@unibo.it Margherita Perricone, email: margherita.perricon2@unibo.it Keywords: JAK2, V617F mutation, allele burden, myeloproliferative neoplasms, MPN Received: June 21, 2016      Accepted: March 20, 2017      Published: March 31, 2017 ABSTRACT Since low JAK2 V617F allele burden (AB) has been detected also in healthy subjects, its clinical interpretation may be challenging in patients with chronic myeloproliferative neoplasms (MPNs). We tested 1087 subjects for JAK2 V617F mutation on suspicion of hematological malignancy. Only 497 (45.7%) patients were positive. Here we present clinical and laboratory parameters of a cohort of 35/497 patients with an AB ≤ 3%. Overall, 22/35 (62.9%) received a WHO-defined diagnosis of MPN and in 14/35 cases (40%) diagnosis was supported by bone marrow (BM) histology (‘’Histology-based’’ diagnosis). In patients that were unable or refused to perform BM evaluation, diagnosis relied on prospective clinical observation (12 cases, 34.3%) and molecular monitoring (6 cases, 17.1%) (‘’Clinical-based’’ or ‘’Molecular-based’’ diagnosis, respectively). In 11/35 (31.4%) patients, a low JAK2 V617F AB was not conclusive of MPN. The probability to have a final hematological diagnosis (ET/PV/MF) was higher in patients with thrombocytosis than in patients with polyglobulia (73.7% vs 57.1%, respectively). The detection of AB ≥ 0.8% always corresponded to an overt MPN phenotype. The repetition of JAK2 V617F evaluation over time timely detected the spontaneous expansion (11 cases) or reduction (4 cases) of JAK2 V617F -positive clones and significantly oriented the diagnostic process. Our study confirms that histology is relevant to discriminate small foci of clonal hematopoiesis with uncertain clinical significance from a full blown disease. Remarkably, our data suggest that a cut-off of AB ≥ 0.8% is very indicative for the presence of a MPN. Monitoring of the AB over time emerged as a convenient and non-invasive method to assess clonal hematopoiesis expansion.