Researchers have discovered a strong correlation between the progression of polycythemia vera (PV) and the presence of an abnormal karyotype (AK) at the time of diagnosis, which could be beneficial in monitoring a patient’s response to disease-modifying therapies and in predicting disease progression.

“The main objective of the current study was to provide a detailed account on the prognostic relevance of abnormal karyotype (AK) and associated specific cytogenetic abnormalities in polycythemia vera (PV),” researchers wrote in Hematologica.

This study assessed data from 669 patients with PV, of whom 436 patients (65%) underwent cytogenetic evaluation within the first year after diagnosis.

Specific Abnormalities & Outcomes With AK

The analysis found that the karyotype was abnormal in 15% of patients, including isolated abnormalities of loss of Y chromosome (-Y; 3%), +9 (3%), del(20q) (2%), and +8 (1%). Researchers noted that AK correlated with older age (P<0.01), lower platelet count (P<0.01), and grade 2 or higher reticulin fi brosis (P<0.01). Specifi cally, del(20q) correlated with older age and grade 2 or higher reticulin fi brosis, and +9 was associated with a higher incidence of a history of venous thrombosis. Further, SRSF2 and IDH2 mutations clustered with normal karyotype, according to the researchers.

Compared with a normal karyotype, the AK was also associated with post-PV fibrotic (MF) transformations (21% vs 10%; P<0.01) and leukemic (LT) transformations (7% vs. 2%; P<0.01). Significance was sustained during multivariable analysis for post-PV MF (HR, 3.7; P<0.01) but not LT. Regarding specific abnormalities, del(20q) was associated with progression to postPV MF, and at least two abnormalities were associated with LT.

Over a median follow-up of 7.4 years, 163 patients (37%) died, 50 patients (11%) experienced progression to post-PV MF, and 14 patients (3%) developed LT.

Potential Use of AK as an Indicator of Risk

Data from univariate analysis revealed that with respect to survival outcomes, abnormal karyotypes were linked to a shorter average lifespan of 10.5 years compared to 16.3 years in those with normal karyotypes (P<0.01). This association persisted in multivariable analysis (HR, 2.0; P=0.02), along with factors such as age (≥60 years), elevated white blood cell counts (≥15 × 10⁹/L), and the presence of an SRSF2 mutation (P<0.01).

“The current study establishes AK at PV diagnosis to be an independent risk factor for survival and post-PV MF/LT,” researchers wrote. “The increased risk of post-PV MF with del (20q), and LT with more than two abnormalities requires confirmation in prospective studies.”