Repeated Molecular Testing Indicates Dynamic Disease Profile in Patients With PV, ET

Careful interpretation of molecular findings is needed in patients with polycythemia vera (PV) and essential thrombocythemia (ET), according to a study published in Frontiers in Oncology. Further research in this field should focus on improving understanding of the disease and improving prognostic tools.

Myeloproliferative neoplasms (MPN) are driven through 3 genes that can have specific mutations. Mutations in some genes have been proposed as a potential disease risk and therefore have been included as a prognostic system for PV and ET. This study aimed to “assess the dynamics of the molecular profile in PV and ET by investigating the occurrence and allelic burden of both driver and passenger mutations at 2 time points.”

Participants for this study came from patients of a hospital in Gdansk, Poland, who had a diagnosis of PV or ET. Patients who received their diagnosis at least 5 years before the study were included. All diagnoses were affirmed with criteria from the World Health Organization. Blood samples were also collected from all participants, which were used to extract genomic DNA. Participants were separated into low, intermediate, and high risk groups.

There were 49 participants in this study from whom 98 samples were analyzed. There were 78 variants found in the 37 genes that were analyzed, of which JAK2 p.Val617Phe, CALR type 1, CALR type 2 and MPL p.Trp515Leu were the most frequent. There were 2 coexisting canonical mutations found in 1 patient and noncanonical variants in driver genes found in 4 patients. There were 3 women who had a JAK2 p.Val617Phe mutation detected at diagnosis but not detected in the follow-up. The researchers found that the mean number of variants was higher among participants who had longer observation times than the median time of 104 months.

There were 26 patients with ET in the low-risk group and 10 in the high-risk group, and 6 and 7 patients with PT, respectively. There was an increase in the mutation-enhanced international prognostic systems score in 2 consecutive samples mediated by age (17 patients in ET, 6 in PV). The second sample put patients in the high-risk group in a maximum of 5 cases in the ET group, which was not found in the PV group. Myelofibrosis (MF) risk in 5 and 10 years was found to be comparable in patients with ET and PV.

Cytoreduction was started in 78% of patients at diagnosis; 20 patients needed a change in treatment and 25 stayed on the treatment in the time between the sample collection. Participants who used hydroxyurea monotherapy had similar rates of developing secondary MF and thrombotic complications, similar numbers of new mutations, mutations overall, and mutations detected on the second sample. A total of 9 patents, 7 with ET and 2 with PV, had fibrotic progression at the second visit. A total of 6 patients experienced thrombosis in the time between samples.

The researchers concluded that careful interpretation of molecular findings are needed to assess specific variants and their pathogenicity. Patients who have been diagnosed with MPNs should be evaluated more than once, as it is insufficient to only evaluate the risk once throughout their diagnosis, especially in younger patients.

Reference

Sobieralski P, Wasag B, Leszczyńska A, Żuk M, Bieniaszewska M. The molecular profile in patients with polycythemia vera and essential thrombocythemia is dynamic and correlates with disease’s phenotype. Front Oncol. Published online August 21, 2023. doi:10.3389/fonc.2023.1224590