Clinical Impact of Allele Burden in Philadelphia-Negative Myeloproliferative Neoplasms.

Objective: The impact of allele burden on clinical course in Philadelphia-negative (Ph-negative) myeloproliferative neoplasms (MPNs) is not clear. We analyzed the clinical impact of allele burden in a relatively large series of patients with Ph-negative MPNs and long-term follow-up.

Materials And Methods: A total of 228 patients with Ph-negative MPNs, including 118 with essential thrombocythemia (ET), 84 with primary myelofibrosis (PMF), and 26 with polycythemia vera (PV), were analyzed. The JAK2 MutaScreen assay was used to quantify allele burden in genomic DNA.

Results: In PV cases, high allele burden was associated with a trend towards inferior overall survival. In ET, high allele burden was associated with lower hemoglobin and hematocrit levels, higher lactate dehydrogenase (LDH) levels, larger spleen size, and increased bleeding and mortality rates. In PMF, high allele burden was associated with higher leukocyte counts and larger spleen size. In the entire cohort, high allele burden was associated with higher leukocyte and lower platelet counts, higher LDH levels, larger spleen size, higher percentage of bleeding events, higher death rate, and inferior overall survival.

Conclusion: Our results suggest that high allele burdens are associated with more severe disease in PV and ET. In PMF, high allele burdens were associated with more pronounced myeloproliferative phenotypes. In Ph-negative MPNs, high allele burdens were associated with more aggressive phenotypes. Our data with a long follow-up period support the possibility of allele burden being used as a marker for predicting clinical phenotype in cases of Ph-negative MPNs.