Impact of Integrated Genetic Information on Diagnosis and Prognostication for Myeloproliferative Neoplasms in the Next-Generation Sequencing Era

Abstract

Since next-generation sequencing has been widely used in clinical laboratories, the diagnosis and risk stratification of hematologic malignancies are greatly dependent on genetic aberrations. In this study, we analyzed the genomic landscapes of 200 patients with myeloproliferative neoplasms (MPNs) and evaluated the impact of the genomic landscape on diagnosis and risk stratification. Mutations in JAK2, CALR and MPL were detected in 76.4% of MPNs. The proportion of patients with clonal genetic markers increased up to 86.4% when all detectable genetic aberrations were included. Significant co-occurring genetic aberrations potentially associated with phenotype and/or disease progression, including those in JAK2/SF3B1 and TP53/del(13q), del(5q), −7/del(7q) and complex karyotypes, were detected. We also identified genetic aberrations associated with patient outcomes: TP53 and −7/del(7q) were associated with an inferior chance of survival, RUNX1, TP53 and IDH1/2 were associated with leukemic transformation and SF3B1, IDH1/2, ASXL1 and del(20q) were associated with fibrotic progression. We compared risk stratification systems and found that mutation-enhanced prognostic scoring systems could identify lower risk polycythemia vera, essential thrombocythemia and higher risk primary myelofibrosis. Furthermore, the new risk stratification systems showed a better predictive capacity for patient outcome. These results collectively indicate that integrated genetic information can enhance diagnosis and prognostication in patients with myeloproliferative neoplasms.

Classification and prognostic stratification based on genomic features in myelodysplastic neoplasms, myeloproliferative neoplasms, and their overlapping conditions

“…DNA samples from peripheral blood or bone marrow at diagnosis were used. Mutation data was obtained using targeted NGS panels as previously described (10,11). We used two versions of the NGS panel depending on the accessed time points.…”

SF3B1 Mutations in Hematological Malignancies

“…Unlike what happens in MDS, in MPNs the SF3B1 mutations appear to increase the risk of fibrotic transformation [33,34]. It has also been suggested that the co-occurrence of SF3B1 and JAK2 or MPL mutations is associated with an increased risk of thrombotic events [35,36].…”

Pathophysiology, classification, and complications of common asymptomatic thrombocytosis in newborn infants

“…The incidence of essential thrombocytosis in newborn infants is not well known. Essential thrombocytosis is represented by megakaryocytic hyperplasia in the bone marrow with thrombocytosis, which is mainly caused by mutations in Janus kinase 2 ( JAK2 ) or myeloproliferative leukemia ( MPL , a TPO receptor gene) [ 27 ]. It is known to increase the risk of vascular events such as hemorrhage and thrombosis due to thrombocytosis.…”