Cytogenetic abnormalities in polycythemia vera: phenotypic correlates and prognostic relevance in 669 informative cases

The main objective of the current study was to provide a detailed account of the prognostic relevance of abnormal karyotype and associated specific cytogenetic abnormalities in polycythemia vera (PV). Six hundred and sixty-nine PV patients were informative, of whom 436 (65%) were evaluated within 1 year of diagnosis. Karyotype abnormalities were found in 67 (15%) patients, including isolated abnormalities of loss of Y chromosome (-Y; N=15; 3%), +9 (N=11; 3%), del(20q) (N=10; 2%), and +8 (N=4; 1%). Abnormal karyotype correlated with older age (P<0.01), lower platelet count (P<0.01), and grade ≥2 reticulin fibrosis (P<0.01). Specifically, del(20q) correlated with older age and grade ≥2 reticulin fibrosis, while +9 correlated with a higher incidence of a history of venous thrombosis. SRSF2 and IDH2 mutations clustered with normal karyotype. At a median follow-up of 7.4 years, 163 (37%) deaths, 50 (11%) cases of fibrotic transformation (post-PV MF) and 14 (3%) cases of leukemic transformation (LT) were documented. In univariate analysis, abnormal karyotype was associated with inferior overall survival (median 10.5 vs. 16.3 years; P<0.01); the statistical significance of this association was sustained in multivariable analysis (hazard ratio=2.0; P=0.02), along with associations with age ≥60 years (P<0.01), leukocytosis ≥15×109/L (P<0.01) and SRSF2 mutation (P<0.01). Abnormal karyotype was also associated with post-PV MF (21% vs. 10%; P<0.01) and LT (7% vs. 2%; P<0.01); the statistical significance of this association was sustained in multivariable analysis for post-PV MF (hazard ratio=3.7; P<0.01), but not for LT (P=0.47). In regard to specific abnormalities, del(20q) was associated with progression to post-PV MF and ≥2 abnormalities with LT. The current study describes the spectrum of cytogenetic abnormalities in PV and their associated phenotypic and prognostic correlates.