RESUMO
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.
Assuntos
Calreticulina/genética , Mutação , Mielofibrose Primária/genética , Trombocitemia Essencial/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Aminoácidos , Substituição de Aminoácidos , Povo Asiático/genética , Sequência de Bases , Feminino , Frequência do Gene , Genótipo , Humanos , Janus Quinase 2/genética , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Fenilalanina/genética , Mielofibrose Primária/etnologia , Receptores de Trombopoetina/genética , Trombocitemia Essencial/etnologia , Valina/genética , Adulto JovemRESUMO
Calreticulin (CALR) mutations were recently identified in patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF) devoid of JAK2 and MPL mutations. We evaluated the clinical, laboratory, and molecular features of a Taiwanese population of patients with ET. Among 147 ET patients, CALR mutations were detected in 33 (22.5 %), JAK2V617F in 94 (63.9 %), and MPL mutations in 4 (2.7 %). Sixteen (10.9 %) patients were negative for all three mutations (CALR, JAK2V617F, and MPL; triple negative). Interestingly, one patient with the type 2 CALR mutation also harbored a low allele burden (0.025 %) of JAK2V617F mutation. Furthermore, we found a novel CALR mutation, with the resultant protein sharing an identical amino acid sequence to the type 6 CALR mutant. Compared to those with JAK2 mutation, CALR-mutated ET patients were characterized by younger age, lower leukocyte count, higher platelet count, and decreased risk of thrombosis. CALR mutations had a favorable impact on thrombosis-free survival (TFS) for ET patients, whereas the respective TFS outcomes were similarly poorer in JAK2-mutated ET and PV patients. Multivariate analysis confirmed that younger age (<60 years), presence of CALR mutations, and a lower platelet count (<1,000 × 10(9)/L) were independently associated with a longer TFS in ET patients. The current study demonstrates that CALR mutations characterize a special group of ET patients with unique phenotypes that are not discrepant from those seen in Western countries.
Assuntos
Calreticulina/genética , Mutação , Trombocitemia Essencial/genética , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Sequência de Aminoácidos , Feminino , Humanos , Janus Quinase 2/genética , Estimativa de Kaplan-Meier , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Fenótipo , Contagem de Plaquetas , Modelos de Riscos Proporcionais , Receptores de Trombopoetina/genética , Alinhamento de Sequência , Deleção de Sequência , Homologia de Sequência de Aminoácidos , Esplenomegalia/etiologia , Taiwan/epidemiologia , Trombocitemia Essencial/complicações , Trombocitemia Essencial/etnologia , Trombocitemia Essencial/mortalidade , Trombofilia/etiologia , Adulto JovemRESUMO
BACKGROUND/AIM: JAK2V617F is an acquired mutation present in a considerable proportion of patients with chronic myeloproliferative disorders. Its reported prevalence in European and US studies of patients with essential thrombocythaemia (ET) is 23-57%. This study was conducted to determine the prevalence of the JAK2 mutation in Asian ET patients, and to examine their disease profile. METHODS: Asian patients with ET were either recruited to the study or registry data were analysed retrospectively. Blood samples were collected for analysis of JAK2 mutation status during routine patient follow up. Clinical data on these patients (including demographics and disease profiles) and complications at diagnosis were recorded. RESULTS: The JAK2 mutation was detected in 35/102 (34%) patients. Females were more likely than males to have JAK2 mutation (P = 0.031). At diagnosis, JAK2-mutated patients were found to be older (P = 0.012), have higher leucocyte counts (P = 0.036) and high-risk disease (P = 0.039). There were no other statistically significant differences between mutated and wild-type JAK2 ET patients. CONCLUSION: The prevalence of JAK2 mutations in this population of Asian ET patients was 34%. Patients with the JAK2 mutation were significantly more likely to have high-risk disease. Further studies are required to assess the role of JAK2 mutations in risk stratification in ET and compare the phenotype of Asian patients with other populations.
