title: A compendium of cytogenetic abnormalities in myelofibrosis: molecular and phenotypic correlates in 826 patients.
abstract: Among 826 patients with primary myelofibrosis (PMF) and analysable metaphases on cytogenetic studies, 352 (42·6%) had abnormal karyotype, of which 240 (68·2%) were sole aberrations and 48 (13·6%) were complex; the most frequent abnormalities were 20q- (23·3%), 13q- (18·2%), +8 (11·1%), +9 (9·9%), chromosome 1q+ (9·7%) and -7/7q- (7·1%). Phenotypic correlates included: abnormal karyotype with anaemia (P = 0·02), leucopenia (P < 0·01) and thrombocytopenia (P < 0·01); complex karyotype with younger age (P = 0·04) and thrombocytopenia (P < 0·01); 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 = 0·3). 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 = 0·02) and U2AF1 (P = 0·01). 13q- was associated with mutant CALR (P = 0·03), +9 with mutant JAK2 (P = 0·02) and 20q- with mutant SRSF2 (P = 0·02). The current PMF study provides detailed cytogenetic information and correlations with mutations and clinical phenotype.
authors.affiliation: Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Emnet
authors.initials: E
authors.lastname: Wassie
authors.forename: Christy
authors.initials: C
authors.lastname: Finke
authors.forename: Naseema
authors.initials: N
authors.lastname: Gangat
authors.forename: Terra L
authors.initials: TL
authors.lastname: Lasho
authors.forename: Animesh
authors.initials: A
authors.lastname: Pardanani
authors.forename: Curtis A
authors.initials: CA
authors.lastname: Hanson
authors.forename: Rhett P
authors.initials: RP
authors.lastname: Ketterling
authors.forename: Ayalew
authors.initials: A
authors.lastname: Tefferi
mesh_terms: D059786:Abnormal Karyotype; D000368:Aged; D000740:Anemia / Q000209:etiology / Q000235:genetics; D002877:Chromosomes, Human / Q000235:genetics*; D005260:Female; D006801:Humans; D007970:Leukopenia / Q000209:etiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D055728:Primary Myelofibrosis / Q000150:complications / Q000235:genetics*; D013921:Thrombocytopenia / Q000209:etiology / Q000235:genetics
keywords: CALR; JAK2; karyotype; myelofibrosis; myeloproliferative