JAK2V617F Allele Burden (AB) in patients with Philadelphia negative Myeloproliferative Neoplasms (MPNS)

PRATTI ARIANAN; OJEDA MARA; VOSS MARIA; BRAGOS IRMA

Rosario

Congreso; XVI Congress-XXXIV Annual Meeting of Rosario Biology Society; 2014

SOCIEDAD DE BIOLOGÍA DE ROSARIO

MPNs are clonal hematopoietic disorders. The most common MPNs are essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF). Many of this patients carry the JAK2V617F activating mutation, that can be harbored in the heterozygous or homozygous state, the latter deriving from mitotic recombination; homozygosity for this mutation is found in some PV and MF patients but it is rare in ET. The gene-dosage hypothesis, postulates a correlation between disease phenotype and the proportion of JAK2V617F mutant alleles. The aim of the study was to quantify the AB of JAK2V617F and correlate it with hematologic and clinical phenotype. We studied 75 patients JAK2V617F: 32 with PV, 29 with TE and 14 with MF. We obtained genomic DNA from patients at diagnosis or those without citorreductive treatment. The AB analysis was performed with the use of two allele specific, quantitative PCR assays to measure either the wild type or mutant allele. The AB was expressed as the percentage of JAK2V617F on total JAK2. We found that the JAK2 (V617F) AB is significantly higher in patients with PV (69%) than in those with ET (38%) (p= 0.0002) and is significantly higher in patients with MF (76%) than in those with ET (38%) (p=0.0001). We analyzed correlations between AB and hematologic parameters. We found a moderate and direct relationship between AB and leukocytes count and a moderate and inverse relationship between AB and platelets count (p