A compendium of cytogenetic abnormalities in myelofibrosis: molecular and phenotypic correlates in 826 patients. (17th December 2014)

• Record Type: Journal Article
• Authors: Wassie, Emnet; Finke, Christy; Gangat, Naseema; Lasho, Terra L.; Pardanani, Animesh; Hanson, Curtis A.; Ketterling, Rhett P.; Tefferi, Ayalew
• Is Part Of: British journal of haematology. Volume 169:Number 1(2015:Apr.)
• Page Start: 71
• Page End: 76
• Publication Date: 2014-12-17
• Subjects: myelofibrosis -- myeloproliferative -- karyotype -- JAK2 -- CALR; Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.13260
• Languages: English
• ISSNs: 0007-1048

Abstract

Summary: 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.