A compendium of cytogenetic abnormalities in myelofibrosis: molecular and phenotypic correlates in 826 patients

Among 826 patients with primary myelofibrosis (PMF) and analysable metaphases on cytogenetic studies, 352 (426%) had abnormal karyotype, of which 240 (682%) were sole aberrations and 48 (136%) were complex; the most frequent abnormalities were 20q- (233%), 13q- (182%), +8 (111%), +9 (99%), chromosome 1q+ (97%) and -7/7q- (71%). Phenotypic correlates included: abnormal karyotype with anaemia (P=002), leucopenia (P<001) and thrombocytopenia (P<001); complex karyotype with younger age (P=004) and thrombocytopenia (P<001); leucopenia with 20q-, +8 and -7/7q- and thrombocytopenia with 20q- and -7/7q-. Cytopenias were less likely to occur with 13q-. 476 patients were annotated for JAK2/CALR/MPL mutations; abnormal karyotype frequencies were 43% in JAK2, 42% CALR, 33% MPL mutated and 34% triple-negative cases (P=03). A proportion of patients were also screened for ASXL1, EZH2, IDH1, IDH2, SRSF2, U2AF1 and SF3B1 mutations; in all instances, mutational frequencies were higher in patients with normal karyotype, reaching significance for ASXL1 (P=002) and U2AF1 (P=001). 13q- was associated with mutant CALR (P=003), +9 with mutant JAK2 (P=002) and 20q- with mutant SRSF2 (P=002). The current PMF study provides detailed cytogenetic information and correlations with mutations and clinical phenotype.