TY - JOUR
T1 - A compendium of cytogenetic abnormalities in myelofibrosis
T2 - Molecular and phenotypic correlates in 826 patients
AU - Wassie, Emnet
AU - Finke, Christy
AU - Gangat, Naseema
AU - Lasho, Terra L.
AU - Pardanani, Animesh
AU - Hanson, Curtis A.
AU - Ketterling, Rhett P.
AU - Tefferi, Ayalew
N1 - Publisher Copyright:
© 2014 John Wiley & Sons Ltd.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - 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.
AB - 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.
KW - CALR
KW - JAK2
KW - Karyotype
KW - Myelofibrosis
KW - Myeloproliferative
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U2 - 10.1111/bjh.13260
DO - 10.1111/bjh.13260
M3 - Article
C2 - 25521305
AN - SCOPUS:84925038218
SN - 0007-1048
VL - 169
SP - 71
EP - 76
JO - British journal of haematology
JF - British journal of haematology
IS - 1
ER -