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

Humans ; Janus Kinase 2 ; Leukemia, Myeloid, Acute ; Mutation ; Thrombocythemia, Essential

OBJECTIVETo detect the activity of autophagy and explore the impact on survival and proliferation of HEL cells and hematopoietic cells of polycythemia vera （PV） patients with JAK2 V617F mutation.

METHODSFlow cytometry, AO staining and Western blot methods were used to detect the autophagy activity and the expression of LC3-Ⅱ protein of JAK2 V617F+ HEL cells and hematopoietic cells of 12 newly diagnosed PV patients with JAK2 V617F mutation. HEL cells and bone marrow cells of 3 PV patients were treated with rapamycin or 3-MA to induce and inhibit autophagy, respectively. CellTiter Glo(R) method was used to detect the proliferation activity of cells.

RESULTSThere was higher level of mean LC3-Ⅱ fluorescence intensity in HEL cells (159 389 ± 29 001) than that in K562 cells (96 047 ± 24 134) (P=0.044). The formation of autophagosome in HEL cells is more than that in K562 cells detected by microscope. What's more, the level of mean LC3-Ⅱ fluorescence intensity in 12 PV patients' myeloid cells (92 842 ± 4 250) was higher than that of 15 healthy volunteers (86 633 ± 2 504) (P=0.001). The expression of LC3-Ⅱ protein was higher in PV patients' peripheral blood cells than that in healthy volunteers detected by Western blot. After treated with rapamycin 12, 24, 48 h, the activity of autophagy in HEL cells and bone marrow cells of 3 PV patients were increased and the proliferation activity was higher than the control group, the proliferation activity at 48 h were (101 413 ± 3 720), (18 744 ± 1 015), respectively. However, after treated with 3-MA 12, 24, 48 h, the activity of autophagy was decreased and the proliferation activity was lower than the control group, the proliferation activity at 48 h were (5 732 ± 166), (5 371 ± 56), respectively.

CONCLUSIONThere is high basical activity of autophagy in JAK2 V617F+ HEL cells and hematopoietic cells of PV patients with JAK2 V617F mutation. Up-regulated autophagy promotes proliferation of JAK2 V617F⁺ HEL cells and bone marrow cells of PV patients with JAK2 V617F mutation. Decreased autophagy inhibits proliferation of JAK2 V617F+ HEL cells and bone marrow cells of PV patients with JAK2 V617F mutation.

Humans ; Thrombocythemia, Essential/therapy* ; Platelet Count ; Janus Kinase 2

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

BACKGROUND: Recently, myeloproliferative leukemia (MPL) W515 mutations have been reported to be molecular markers for myeloproliferative neoplasms (MPNs). We studied the association between MPL W515 mutations and the clinico-hematological features of patients with MPNs. METHODS: Our study included 154 consecutive patients diagnosed with MPNs (31 had polycythemia vera [PV]; 106, essential thrombocythemia [ET]; and 17, primary myelofibrosis [PMF]). MPL W515 mutations were detected by real-time PCR and direct sequencing methods. RESULTS: The MPL W515L mutation was found in 4 patients and the MPL W515A mutation was detected in 1 patient. These 5 patients were diagnosed with JAK2 V617F-negative ET, and they accounted for 12.5% of patients with JAK2 V617F-negative ET. The patients with MPL W515-positive ET showed significantly lower hemoglobin levels and WBC counts than did patients with MPL W515-negative ET or JAK2 V617F-positive ET. CONCLUSIONS: MPL W515 mutation is a useful diagnostic marker for JAK2 V617F-negative MPNs and it is associated with specific hematologic characteristics such as lower hemoglobin levels and WBC counts.
Humans ; Janus Kinase 2 ; Leukemia ; Polycythemia Vera ; Primary Myelofibrosis ; Real-Time Polymerase Chain Reaction ; Thrombocythemia, Essential

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

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

JAK2V617F is a novel oncogene involved in myeloproliferative neoplasms (MPN) and closely related to its vascular complications. Recent researches found the vascular endothelial injury in patients with MPN. It is increasingly being recognized that endothelial cells and endothelial progenitor cells (EPC) play an important role in MPN. Here, the pathogenesis of the EPC JAK2V617F mutation and peripheral blood EPC counts in patients with MPN or with vascular complications are reviewed.
Endothelial Cells ; Endothelial Progenitor Cells ; Humans ; Janus Kinase 2 ; Mutation ; Myeloproliferative Disorders

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