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A compendium of cytogenetic abnormalities in myelofibrosis: molecular and phenotypic correlates in 826 patients
Author(s) -
Wassie Emnet,
Finke Christy,
Gangat Naseema,
Lasho Terra L.,
Pardanani Animesh,
Hanson Curtis A.,
Ketterling Rhett P.,
Tefferi Ayalew
Publication year - 2015
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13260
Subject(s) - myelofibrosis , karyotype , biology , cytogenetics , medicine , gastroenterology , pathology , genetics , chromosome , bone marrow , gene
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 JAK 2 / CALR / MPL mutations; abnormal karyotype frequencies were 43% in JAK 2 , 42% CALR , 33% MPL mutated and 34% triple‐negative cases ( P = 0·3). A proportion of patients were also screened for ASXL 1 , EZH 2 , IDH 1 , IDH 2 , SRSF 2 , U2 AF 1 and SF 3B1 mutations; in all instances, mutational frequencies were higher in patients with normal karyotype, reaching significance for ASXL 1 ( P = 0·02) and U2 AF 1 ( P = 0·01). 13q− was associated with mutant CALR ( P = 0·03), +9 with mutant JAK 2 ( P = 0·02) and 20q− with mutant SRSF 2 ( P = 0·02). The current PMF study provides detailed cytogenetic information and correlations with mutations and clinical phenotype.