INT113161

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Context Info
Confidence 0.77
First Reported 2003
Last Reported 2009
Negated 1
Speculated 0
Reported most in Body
Documents 50
Total Number 53
Disease Relevance 42.52
Pain Relevance 4.76

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

cell differentiation (Jak2) cytosol (Jak2) signal transduction (Jak2)
histone binding (Jak2) cytoskeleton (Jak2) nucleus (Jak2)
Anatomy Link Frequency
spleen 6
bone marrow 4
platelet 4
megakaryocytes 2
erythrocytes 1
Jak2 (Mus musculus)
Jak2 - V617F (20)
Pain Link Frequency Relevance Heat
fibrosis 201 99.50 Very High Very High Very High
cerebral cortex 104 99.28 Very High Very High Very High
Hippocampus 108 99.12 Very High Very High Very High
GABAergic 28 99.08 Very High Very High Very High
gABA 70 95.44 Very High Very High Very High
cytokine 122 95.36 Very High Very High Very High
antagonist 2 92.88 High High
Parenteral administration 52 92.16 High High
tetrodotoxin 2 91.20 High High
depression 4 89.76 High High
Disease Link Frequency Relevance Heat
Disease 458 100.00 Very High Very High Very High
Myelodysplastic Syndromes 2523 99.96 Very High Very High Very High
Sprains And Strains 395 99.82 Very High Very High Very High
Erythrocytosis 1173 99.66 Very High Very High Very High
Myelofibrosis 655 99.64 Very High Very High Very High
Splenomegaly 207 99.56 Very High Very High Very High
Fibrosis 189 99.50 Very High Very High Very High
Myeloproliferative Disorder 263 99.36 Very High Very High Very High
Congenital Anomalies 276 99.32 Very High Very High Very High
Leukocytosis 162 99.04 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
We expressed murine JAK2 WT or V617F via retroviral bone marrow transduction/transplantation in the hematopoietic system of two different inbred mouse strains, Balb/c and C57Bl/6 (B6).
Gene_expression (expressed) of JAK2 in hematopoietic system associated with sprains and strains
1) Confidence 0.77 Published 2006 Journal PLoS ONE Section Abstract Doc Link PMC1762384 Disease Relevance 1.18 Pain Relevance 0
In our model, robust polycythemia is induced by modest overexpression of JAK2 V617F in BM with two normal JAK2 genes, but further studies will be necessary to determine whether the phenotype is influenced by levels of normal JAK2.
Gene_expression (overexpression) of JAK2 V617F (V617F) associated with erythrocytosis
2) Confidence 0.77 Published 2006 Journal PLoS ONE Section Body Doc Link PMC1762384 Disease Relevance 1.04 Pain Relevance 0
The fact that the central erythroid features of PV are recapitulated by expression of JAK2 V617F argues that it is the primary and direct cause of human PV.


Gene_expression (expression) of JAK2 V617F (V617F) associated with myelodysplastic syndromes
3) Confidence 0.77 Published 2006 Journal PLoS ONE Section Body Doc Link PMC1762384 Disease Relevance 0.95 Pain Relevance 0
Platelet counts were not affected in either strain despite expression of JAK2 V617F in megakaryocytes and markedly prolonged tail bleeding times.
Gene_expression (expression) of JAK2 V617F (V617F) in Platelet associated with hemorrhage and sprains and strains
4) Confidence 0.77 Published 2006 Journal PLoS ONE Section Abstract Doc Link PMC1762384 Disease Relevance 1.63 Pain Relevance 0.04
There are no JAK2 inhibitors in clinical use, but the isoquinolinone compound JAK inhibitor I [15], [32] and the tyrphostin AG-490 [33] both inhibited the proliferation of Ba/F3 cells expressing JAK2 V617F with an IC50 of 0.3 and 3.5 µM, respectively (Figure 7B).
Gene_expression (expressing) of JAK2 V617F (V617F)
5) Confidence 0.77 Published 2006 Journal PLoS ONE Section Body Doc Link PMC1762384 Disease Relevance 0.48 Pain Relevance 0.09
There was modest (2- to 3-fold) overexpression of JAK2 in both cohorts, relative to the level of endogenous JAK2 protein (Figure 4A).
Gene_expression (overexpression) of JAK2
6) Confidence 0.77 Published 2006 Journal PLoS ONE Section Body Doc Link PMC1762384 Disease Relevance 0 Pain Relevance 0
Increased expression of JAK2 V617F in patients with homozygous mutations may increase severity of the phenotype in PV [41], perhaps because the mutant and WT JAK2 kinases compete for Epo receptor binding [13].
Gene_expression (expression) of JAK2 V617F (V617F) associated with myelodysplastic syndromes
7) Confidence 0.77 Published 2006 Journal PLoS ONE Section Body Doc Link PMC1762384 Disease Relevance 0.86 Pain Relevance 0.06
In the initial report, retroviral expression of JAK2 V617F in murine BM induced erythrocytosis in transplanted recipient mice [13], but the syndrome was not characterized further.
Gene_expression (expression) of JAK2 V617F (V617F) associated with syndrome and erythrocytosis
8) Confidence 0.77 Published 2006 Journal PLoS ONE Section Body Doc Link PMC1762384 Disease Relevance 0.87 Pain Relevance 0.15
Together, these results indicate that JAK2 V617F expression directly induces polycythemia in mice through Epo-independent overproduction of erythrocytes.
Gene_expression (expression) of JAK2 V617F (V617F) in erythrocytes associated with erythrocytosis
9) Confidence 0.77 Published 2006 Journal PLoS ONE Section Body Doc Link PMC1762384 Disease Relevance 0.88 Pain Relevance 0
These results suggest that JAK2 V617F expression induces myelofibrosis, but the resulting impairment of erythropoiesis is due to a defect of the hematopoietic microenvironment, rather than a deficiency of malignant hematopoietic stem cells.


Gene_expression (expression) of JAK2 V617F (V617F) in hematopoietic stem cells associated with malignant neoplastic disease and myelofibrosis
10) Confidence 0.77 Published 2006 Journal PLoS ONE Section Body Doc Link PMC1762384 Disease Relevance 1.45 Pain Relevance 0.04
Despite the lack of effect on platelet number, JAK2 V617F expression caused profound abnormalities of megakaryocyte maturation and platelet function, manifested by small megakaryocytes, abnormal mitoses during proplatelet formation, and a markedly prolonged tail bleeding time.
Gene_expression (expression) of JAK2 V617F (V617F) in megakaryocytes associated with congenital anomalies and hemorrhage
11) Confidence 0.77 Published 2006 Journal PLoS ONE Section Body Doc Link PMC1762384 Disease Relevance 1.39 Pain Relevance 0
In contrast to the polycythemia, the effects of JAK2 V617F expression on leukocyte and platelet counts were more variable.
Gene_expression (expression) of JAK2 V617F (V617F) in platelet associated with erythrocytosis
12) Confidence 0.77 Published 2006 Journal PLoS ONE Section Body Doc Link PMC1762384 Disease Relevance 1.05 Pain Relevance 0
JAK2 V617F expression did not affect the platelet count in either strain (Figure 2C), despite evidence of proviral expression of GFP in megakaryocytes (Figure 2D).
Gene_expression (expression) of JAK2 V617F (V617F) in platelet associated with sprains and strains
13) Confidence 0.77 Published 2006 Journal PLoS ONE Section Body Doc Link PMC1762384 Disease Relevance 1.39 Pain Relevance 0
That is, if JAK2V617F –expressing erythroid, myeloid and megakaryocytic lineages in PV compete in the marrow space, then splenectomy could limit pathologic expansion.
Gene_expression (expressing) of JAK2V617F associated with myelodysplastic syndromes
14) Confidence 0.75 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2749451 Disease Relevance 0.71 Pain Relevance 0.04
The JAK2V617F mutation can indeed be detected in the spleen as well as BM in patients with PV, and clonality suggests an origin in bone marrow [23].
Gene_expression (detected) of JAK2V617F in bone marrow associated with myelodysplastic syndromes
15) Confidence 0.75 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2749451 Disease Relevance 1.47 Pain Relevance 0.12
JAK2V617F is present in only about half of PMF and post-ET MF patients, but in the vast majority of post-PV MF patients (Tefferi et al 2005).
Gene_expression (present) of JAK2V617F associated with myelodysplastic syndromes and myelofibrosis
16) Confidence 0.75 Published 2007 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2721304 Disease Relevance 0.74 Pain Relevance 0.04
This coincided with a gradual but marked increase in fibrosis in the BM and spleen of JAK2 V617F recipients that was not observed in JAK2 WT recipients (Figure 5B).
Gene_expression (recipients) of JAK2 V617F (V617F) in spleen associated with fibrosis
17) Confidence 0.67 Published 2006 Journal PLoS ONE Section Body Doc Link PMC1762384 Disease Relevance 1.10 Pain Relevance 0.05
This coincided with a gradual but marked increase in fibrosis in the BM and spleen of JAK2 V617F recipients that was not observed in JAK2 WT recipients (Figure 5B).
Gene_expression (recipients) of JAK2 in spleen associated with fibrosis
18) Confidence 0.67 Published 2006 Journal PLoS ONE Section Body Doc Link PMC1762384 Disease Relevance 1.11 Pain Relevance 0.05
Interestingly, polycythemia and reticulocytosis were efficiently resurrected in secondary mice by transplantation of BM and/or spleen cells from primary JAK2 V617F recipients, and this was equally true for donors harvested in the early, polycythemic phase of the disease as well as the later, myelofibrotic phase (Figure 5C).
Gene_expression (recipients) of JAK2 V617F (V617F) in spleen associated with reticulocytosis, erythrocytosis and disease
19) Confidence 0.67 Published 2006 Journal PLoS ONE Section Body Doc Link PMC1762384 Disease Relevance 1.35 Pain Relevance 0.04
There are no JAK2 inhibitors in clinical use, but the isoquinolinone compound JAK inhibitor I [15], [32] and the tyrphostin AG-490 [33] both inhibited the proliferation of Ba/F3 cells expressing JAK2 V617F with an IC50 of 0.3 and 3.5 µM, respectively (Figure 7B).
Gene_expression (expressing) of JAK2
20) Confidence 0.67 Published 2006 Journal PLoS ONE Section Body Doc Link PMC1762384 Disease Relevance 0.50 Pain Relevance 0.09

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