Myeloproliferative neoplasms (MPN) are clonal hematopoietic stem cell diseases characterized by proliferation of one or more myeloid cell lineages in the bone marrow and increased mature and immature cells in peripheral blood. As the most important discovery in recent studies of MPN, JAk2V617F mutation is considered to closely relate with the pathogenesis of MPN. The mutated JAK2 lost self-inhibition, and then, the sustained activation leads to a series of disorders in downstream signal transduction pathways, eventually resulting in malignant cell proliferation. A variety of methods have been used in quantitative/qualitative detection of JAK2V617F mutation, and researches about JAK2V617F mutation and its clinical features have also made some progress. However, it must be noted that there are still some unsolved problems, such as the role of JAk2V617F mutation in pathogenesis of MPN needs further exploration, effective targeted therapy for JAK2 is a attractive topic, and the application of JAK2V617F mutation in disease diagnosis also requires a deep research. In this review, the latest progress from different aspects is summarized briefly, including JAK2 and JAK2V617F mutation, effects of JAK2V617F mutation on the pathogenesis, clinical correlation of JAK2V617F with MPN, and targeting therapy.
Humans ; Janus Kinase 2 ; genetics ; Mutation ; Myeloproliferative Disorders ; genetics ; pathology

Classical myeloproliferative neoplasm (MPN) related thrombosis mainly affects elderly patients and often involves arterial circulation, while, MPN-visceral venous thrombosis (SVT) mainly affects young women, and is closely associated with JAK2V617F mutation but not closely with CALR mutation. The pathogenesis of MPN-SVT is not only related to JAK2V617F mutation and vascular endothelial damage, but also needs further research to determine the machanism. JAK2V617F mutation is the most common in MPN-SVT clinically. Patients with non-cirrhotic SVT need to detect MPN mutation, while the detection of CALR or MPL mutation needs to be combined with clinical judgment. At present, the main treatment strategies of MPN-SVT are JAK inhibitors, supplementation of anticoagulants and treatment of portal hypertension. This article reviews the latest research progress on the epidemiology, pathogenesis, diagnosis and treatment strategies of MPN-SVT.
Aged ; Anticoagulants ; Female ; Humans ; Janus Kinase 2/genetics* ; Janus Kinase Inhibitors ; Mutation ; Myeloproliferative Disorders/genetics* ; Neoplasms ; Thrombosis ; Venous Thrombosis

This study was purposed to investigate the feasibility of high resolution melting (HRM) in the detection of JAK2V617F mutation in patients with myeloproliferative neoplasm (MPN). The 29 marrow samples randomly selected from patients with clinically diagnosed MPN from January 2008 to January 2011 were detected by HRM method. The results of HRM analysis were compared with that detected by allele specific polymerase chain reaction (AS-PCR) and DNA direct sequencing. The results showed that the JAK2V617F mutations were detected in 11 (37.9%, 11/29) cases by HRM, and its comparability with the direct sequencing result was 100%. While the consistency of AS-PCR with the direct sequencing was moderate (Kappa = 0.179, P = 0.316). It is concluded that the HRM analysis may be an optimal method for clinical screening of JAK2V617F mutation due to its simplicity and promptness with a high specificity.
Bone Marrow Neoplasms ; genetics ; Female ; Humans ; Janus Kinase 2 ; genetics ; Male ; Mutation ; Myeloproliferative Disorders ; genetics

The key molecular events in the pathogenesis of myeloproliferative disorders (MPD) have been poorly defined to date, except the case of chronic myeloid leukaemia with the associated rearranged gene bcr/abl. In recent years, a number of different studies described the detection of JAK2 V617F mutation in haematopoietic cells from polycythemia vera patients and other MPDs, which indicates that it plays an important role in the pathogenesis of MPDs. In this review, the JAK2 V617F point mutation and its detection methods, its clinical correlations with MPDs and other malignant hepatopathies were summarized.
Humans ; Janus Kinase 2 ; genetics ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; Myeloproliferative Disorders ; genetics

Adult ; Aged ; Altitude ; Humans ; Janus Kinase 2 ; genetics ; Male ; Middle Aged ; Point Mutation ; Polycythemia ; genetics

Chronic myeloproliferative disease (CMPD) is a group of malignant blood disorders including polycythemia vera, essential thrombocythemia, primary myelofibrosis, chronic myeloid leukemia, and so on. CMPD is characterized by proliferation of one or several lineages in hematopoietic system. The pathogenesis of CMPD is not clear except chronic myeloid leukemia associated with the bcr/abl fusion gene. In recent years, more studies demonstrated that CMPD have a higher mutation rate of gene jak2. In this review, the association of jak2 gene mutation with clinical diagnosis, clinical feature and molecular target therapy in CMPD and other hematological disease were summarized.
Chronic Disease ; Humans ; Janus Kinase 2 ; genetics ; Mutation ; Myelodysplastic-Myeloproliferative Diseases ; genetics

OBJECTIVE: To investigate the clinical characteristics of essential thrombocytopenia (ET) patients with positive mutations including JAK2, CALR, MPL, or negative mutations. METHODS: A total of 66 newly diagnosed ET cases from January 2016 to December 2018 in Department of Hematology, Huaian No.1 People's Hospital affiliated to Nanjing Medical University were analyzed. Statistical analysis data included the patient's sex, age, symptoms, thrombosis and embolism events, spleen omegaly, platelet count (Plt), leukocyte (WBC) count, hemoglobin (Hb), fibrinogen (FIB), thrombus elastic diagram (TEG), serum potassium, blood glucose (GLU), lactate dehydrogenase (LDH), JAK2, CALR and MPL mutations, treatment options, and efficacy. RESULTS: All the patients were not MPL-positive, and divided in three groups: JAK2 mutation (46 cases, 69.7%), CALR mutation (9 cases, 13.6%) and gene negative mutation (11 cases, 16.7%) group. The average age of patients in the JAK2 mutation group was 63.2 years old, and significantly higher than that in the CALR mutation group (51.8 year) and gene negative group (50.2 year) (P＜0.05). Compared with the JAK2 mutation group and gene negative group, the CALR mutation group had lower WBC count (6.3×10/L vs 13.79×10/L) (P=0.003) (6.3×10/L vs 9.70×10/L) (P=0.009). Also the Hb level of patients in CALR mutation group was lower than the JAK2 mutation group (121.22 g/L vs 136.2 g/L) (P=0.036). However, there was higher tumor burden in the CALR mutation group, compared with the gene negative mutation group (300.11 U/L vs 227.4 U/L) (P=0. 033). There was no significant difference among the three groups, such as the Plt counts, serum potassium level, GLU level and FIB level (P＞0.05). In addition, thrombus and embolism appeared in 30.3% (20/66) cases. 18.2% (12/66) cases were complicated with hyperkalemia, which significantly correlated with Plt counts (r=0.518). TEG was performed in 34 patients, of which 41.2% (14/34) had abnormal TEG and 55.9% (19/34) were accompanied by Plt count ＞ 1 000 ×10/L, but there was no significant correlation between them (r=0.134). After routine clinical treatment, all the 66 cases achieved partial or complete hematological remission, but the disease usually repeated. Until now 4.5% (3/66) cases had been converted to myelofibrosis (MF) all with JAK2 mutation, but without advancing to acute myeloid leukemia. CONCLUSION ET patients with JAK2 mutation have higher incidence, moreover were in older age. However, the patients with CALR mutations display lower WBC count and Hb level, but higher tumor burden. In short, the multiple gene mutations of ET showed different clinical features closely relates with the prognosis, thus providing guidance for the clinical diagnosis and treatment.
Aged ; Calreticulin ; genetics ; Humans ; Janus Kinase 2 ; genetics ; Middle Aged ; Mutation ; Primary Myelofibrosis ; Thrombocythemia, Essential ; Thrombocytopenia

OBJECTIVE: To investigate the relationship between JAK2 gene mutation and clinical indicators in patients with myeloproliferative neoplasms (MPN). METHODS: 122 MPN patients in the Department of Hematology, Xiyuan Hospital, China Academy of Chinese Medical Sciences from September 2017 to January 2020 were retrospectively analyzed. The relationship between JAK2 gene mutation and sex, age, peripheral blood cell count, splenomegaly, and thrombosis and bleeding events were analyzed. RESULTS: In 122 patients with MPN, the patients with polycythemia vera (PV) accounted for 36 (29.5%), the patients with essential thrombocythemia (ET) accounted for 56 (45.9%), the patients with myelofibrosis (MF) accounted for 30 (24.6%). The JAK2 gene mutation rate in MPN patients was 64.6% (79/122), and the JAK2 gene mutation rate in PV, ET and MF groups were 77.7% (28/36), 60.7% (34/56) and 56.7% (17/30), the JAK2 gene mutation rate of the patients in PV group was statistically significant as compared with those in the ET group (P＜0.05). The hemoglobin (Hb) count of the patients in JAK2 gene mutation group was higher than those in wild-type group ［(150.0±39.6)g/L vs (129.4±38.9)g/L, P＜0.05］; the white blood cell (WBC) count of the patients in JAK2 gene mutation group was higher than those in the wild type group ［(9.5±4.7)×10 CONCLUSION The mutation rate of JAK2 gene in MPN patients is higher, and the mutation rate of JAK2 gene in PV patients is higher than that in ET and MF patients; JAK2 gene mutations in MPN patients are related to hemogram index; the incidence of splenomegaly is the highest in MF patients, and splenomegaly is related to the occurrence of JAK2 gene mutations in MF patients.
Humans ; Janus Kinase 2/genetics* ; Mutation Rate ; Myeloproliferative Disorders/genetics* ; Polycythemia Vera ; Retrospective Studies

In 2008, WHO made the JAK2V617F gene mutation as one of the specific molecular diagnostic markers of BCR/ABL-negative myeloproliferative neoplasms (MPN). In 2013 two research teams demonstrated that whole genome sequencing technology (WGS) was used to detect calreticulin gene mutation in essential thrombocythaemia (ET) and primary myelofibrosis (PMF) patients with JAK2V617F⁻ and MPL⁻ mutations. In this review, the relationship of CALR gene mutation with MPN is briefly summarized.
Bone Marrow Neoplasms ; genetics ; Calreticulin ; genetics ; Humans ; Janus Kinase 2 ; genetics ; Mutation ; Myeloproliferative Disorders ; genetics ; Receptors, Thrombopoietin ; genetics

Somatic gene V617F mutation in JAK2 is a critical molecular and biological indicator to diagnosis of chronic myeloproliferative disease (MPD). This study was aimed to investigate the genetic background of V617F mutation in 46/1 gene haplotype in Chinese MPD patients, and the frequencies of 46/1 gene haplotype and V617F mutation in three nationalities of Chinese populations. Peripheral blood or bone marrow samples of 150 V617F mutation positive MPD patients, 123 V617F mutation negative MPD patients, 124 healthy Han individuals, 395 healthy Tibetan individuals and 315 healthy Yugu individuals were collected. The allele-specific multiplex PCR method was established, the presence or absence of V617F mutation, the presence or absence of 46/1 haplotype, and the relationship between V617F and 46/1 haplotype were easily identified by agarose gel image. The results showed that the V617F mutation located in the 46/1 haplotype of 88 cases (58.67) among 150 V617F-positive MPD cases. In 814 Chinese healthy individuals including Han, Tibetan, Yugu nationalities, the frequency of the 46/1 gene haplotype was 38.37 without difference in the frequency among different nationalities, and no V617F mutation was found in Chinese healthy populations, The frequency of the 46/1 gene haplotype was 43.09 in V617F mutation negative MPD patients and was 69.33 in V617F mutation positive MPD patients, the latter was obviously higher than former and than that in healthy Han individuals. In conclusion, a multiplex PCR method has been developed that is simple and useful to identify V617F mutation in JAK2 gene and its relationship to the 46/1 haplotype. In more than half of Chinese V617F-positive MPD patients, the V617F mutation locates in 46/1 haplotype in JAK2. The frequencies of 46/1 haplotype are statistically insignificant among Han, Tibetan and Yugu nationality populations.
Asian Continental Ancestry Group ; genetics ; Ethnic Groups ; genetics ; Female ; Haplotypes ; Humans ; Janus Kinase 2 ; genetics ; Male ; Mutation ; Myeloproliferative Disorders ; genetics