Frequency and allele burden of CALR mutations in Chinese with essential thrombocythemia and primary myelofibrosis without JAK2(V617F) or MPL mutations.
CALR mutations are detected in about 50% of persons of predominately European descent with essential thrombocythemia (ET) or primary myelofibrosis (PMF) with wild-type alleles of JAK2 and MPL. We studied 1088 Chinese with diverse myeloproliferative neoplasms including ET (N=234) and PMF (N=50) without JAK2(V617F) or MPL exon 10 mutations. CALR mutation was detected in 53% (95% CI, 46-60%) of subjects with ET and 56% (95% CI, 41-70%) of subjects with PMF. 152 CALR mutations were identified clustering into 15 types including deletions (N=8), insertions (N=3) and complex indels (N=4). We also identified 9 new mutations. Mean (±SD) mutant allele burden was 31±12% (range, 0.5-69%). Persons with PMF had higher CALR mutant allele burdens than those with ET (38±8% vs. 29±12%; P<0.001). Amongst persons with CALR mutations, those with PMF had different clinical features from those with ET. These data may be useful for diagnosing ET and PMF in Chinese who are about 40% of all persons with ET and PMF and for monitoring therapy-response. They also highlight similarities and differences in CALR mutations between Chinese and persons of predominately European descent with these diseases.
Peking University People's Hospital and Institute of Hematology, 11 Xi-Zhi-Men South Street, Beijing 100044, China.
Ning
N
Li
Peking University People's Hospital and Institute of Hematology, 11 Xi-Zhi-Men South Street, Beijing 100044, China.
Qiu-Mei
QM
Yao
Haematology Research Center, Division of Experimental Medicine, Department of Medicine, Imperial College London, W12 OHS London, United Kingdom.
Robert Peter
RP
Gale
Peking University People's Hospital and Institute of Hematology, 11 Xi-Zhi-Men South Street, Beijing 100044, China.
Jin-Lan
JL
Li
Peking University People's Hospital and Institute of Hematology, 11 Xi-Zhi-Men South Street, Beijing 100044, China.
Ling-Di
LD
Li
Peking University People's Hospital and Institute of Hematology, 11 Xi-Zhi-Men South Street, Beijing 100044, China.
Xiao-Su
XS
Zhao
Peking University People's Hospital and Institute of Hematology, 11 Xi-Zhi-Men South Street, Beijing 100044, China.
Hao
H
Jiang
Peking University People's Hospital and Institute of Hematology, 11 Xi-Zhi-Men South Street, Beijing 100044, China.
Qian
Q
Jiang
Peking University People's Hospital and Institute of Hematology, 11 Xi-Zhi-Men South Street, Beijing 100044, China.
Bin
B
Jiang
Peking University People's Hospital and Institute of Hematology, 11 Xi-Zhi-Men South Street, Beijing 100044, China.
Hong-Xia
HX
Shi
Peking University People's Hospital and Institute of Hematology, 11 Xi-Zhi-Men South Street, Beijing 100044, China.
Shan-Shan
SS
Chen
Peking University People's Hospital and Institute of Hematology, 11 Xi-Zhi-Men South Street, Beijing 100044, China.
Kai-Yan
KY
Liu
Peking University People's Hospital and Institute of Hematology, 11 Xi-Zhi-Men South Street, Beijing 100044, China.
Xiao-Jun
XJ
Huang
Peking University People's Hospital and Institute of Hematology, 11 Xi-Zhi-Men South Street, Beijing 100044, China. Electronic address: ruanguorui@pkuph.edu.cn.
Guo-Rui
GR
Ruan
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D037282:Calreticulin / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010649:Phenylalanine / Q000235:genetics; D055728:Primary Myelofibrosis / Q000208:ethnology / Q000235:genetics*; D053628:Receptors, Thrombopoietin / Q000235:genetics; D013920:Thrombocythemia, Essential / Q000208:ethnology / Q000235:genetics*; D014633:Valine / Q000235:genetics; D055815:Young Adult
C576483:CALR protein, human; D037282:Calreticulin; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D010649:Phenylalanine; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D014633:Valine
Allele burden; Calreticulin; Mutation; Myeloproliferative neoplasm