Comparison of JAK2 V617F -positive essential thrombocythaemia and early primary myelofibrosis: The impact of mutation burden and histology.

An accurate histological diagnosis may distinguish essential thrombocythaemia (ET) from early primary myelofibrosis (early-PMF), which is associated with worse outcome. Outcome of ET is also negatively affected by the presence of the JAK2(V617F) mutation. To investigate the impact of JAK2(V617F) mutation burden and histology on outcome, we collected 475 WHO-diagnosed ET (69.2%) or early-PMF JAK2(V617F)-positive patients followed in 4 Italian haematology centers. JAK2(V617F) allele burden was 50% in 90% and 87% of ET and early-PMF patients, respectively (P=.34). During follow-up, 32 (9.7%) ET and 18 (12.3%) early-PMF patients experienced 59 thrombotic events, and 27 patients (5.6%) and 6 (1.2%) patients evolved to myelofibrosis and acute leukemia, respectively. At last contact, 28 (5.8%) patients had died. In early-PMF compared to ET, the 10-year mortality rates (6.7% and 4.3%, P=.73), leukemic transformation rates (1.4% and 1.2%, P=.45), and thrombosis rates (16.7% and 12.2%, P=.12) were comparable. Only progression to overt myelofibrosis at 10years was significantly worse (11.4% and 1.5%, P=.004). In multivariate analysis, a higher (>50%) JAK2(V617F) burden was significantly correlated with fibrotic progression and histology. Considering JAK2(V617F)-positive disease, a higher (>50%) JAK2(V617F) burden and histological classification are independent prognostic risk factors for disease progression. These findings reinforce the need for standardized detection of this mutation.