INT199557

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Context Info
Confidence 0.68
First Reported 2006
Last Reported 2009
Negated 0
Speculated 0
Reported most in Body
Documents 6
Total Number 9
Disease Relevance 4.21
Pain Relevance 0.30

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

cytosol (Bcr) signal transduction (Bcr) plasma membrane (Bcr)
intracellular (Bcr) enzyme binding (Bcr) kinase activity (Bcr)
Anatomy Link Frequency
plasma 2
32D 2
Bcr (Mus musculus)
Pain Link Frequency Relevance Heat
Potency 33 95.24 Very High Very High Very High
Kinase C 1 83.88 Quite High
adenocard 1 49.52 Quite Low
cytokine 8 18.08 Low Low
headache 15 5.00 Very Low Very Low Very Low
pruritus 10 5.00 Very Low Very Low Very Low
Central nervous system 9 5.00 Very Low Very Low Very Low
Pain 4 5.00 Very Low Very Low Very Low
backache 4 5.00 Very Low Very Low Very Low
tolerance 3 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Genetic Translocation 1 99.72 Very High Very High Very High
Philadelphia Chromosome 89 99.52 Very High Very High Very High
Myeloid Leukemia 390 98.88 Very High Very High Very High
Chronic Myeloid Leukemia 13 96.88 Very High Very High Very High
Cancer 48 92.88 High High
Leukemia 98 92.72 High High
Malignant Neoplastic Disease 11 89.24 High High
Acute Myeloid Leukemia 4 88.80 High High
Renal Cell Carcinoma 50 76.88 Quite High
Disease 92 71.04 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Other mechanisms of imatinib resistance may include: increased expression of Bcr-Abl through genomic amplification (Nicolini et al 2006), overexpression of Lyn or other Src-family tyrosine kinases (Donato et al 2003; Dai et al 2004), or overexpression of drug efflux proteins such as P-glycoprotein, which may decrease the intracellular concentration of imatinib in leukemic cells (Thomas et al 2004).
Positive_regulation (increased) of Gene_expression (expression) of Bcr-Abl
1) Confidence 0.68 Published 2008 Journal Drug design, development and therapy Section Body Doc Link PMC2761189 Disease Relevance 0.05 Pain Relevance 0
This translocation fuses the genes encoding BCR and ABL, resulting in expression of the constitutively active protein tyrosine kinase, BCR-ABL.
Positive_regulation (resulting) of Gene_expression (expression) of BCR-ABL
2) Confidence 0.57 Published 2008 Journal OncoTargets and therapy Section Body Doc Link PMC2994207 Disease Relevance 1.51 Pain Relevance 0
Several mechanisms may contribute to imatinib resistance, including increased expression of BCR-ABL kinase through gene amplification, decreased intracellular drug concentrations caused by drug efflux proteins (OCT1), clonal evolution, or over-expression of Src kinases (Lyn, Hck) involved in BCR-ABL independent activation of alternative pathways (Apperley 2007).
Positive_regulation (increased) of Gene_expression (expression) of BCR-ABL
3) Confidence 0.57 Published 2008 Journal OncoTargets and therapy Section Body Doc Link PMC2994207 Disease Relevance 0.08 Pain Relevance 0
A model of nilotinib in complex with Abl kinase mutant M351T showed that the sensitivity of Bcr-Abl mutants to nilotinib segregates into 4 categories: high (IC50 < 70 nmol/L: M244V, G250E, Q252H, F3llL, F317L, M351T, V379I, L387M, H396P, H396R), medium (IC50 < 200 nmol/L: Y253F, E255K, F359V), low (IC50 < 450 nmol/L: Y253H, E255V), and insensitive (IC50 > 2 ?
Positive_regulation (with) of Gene_expression (sensitivity) of Bcr-Abl
4) Confidence 0.49 Published 2008 Journal Drug design, development and therapy Section Body Doc Link PMC2761189 Disease Relevance 0 Pain Relevance 0.09
A model of nilotinib in complex with Abl kinase mutant M351T showed that the sensitivity of Bcr-Abl mutants to nilotinib segregates into 4 categories: high (IC50 < 70 nmol/L: M244V, G250E, Q252H, F3llL, F317L, M351T, V379I, L387M, H396P, H396R), medium (IC50 < 200 nmol/L: Y253F, E255K, F359V), low (IC50 < 450 nmol/L: Y253H, E255V), and insensitive (IC50 > 2 ?
Positive_regulation (mutants) of Gene_expression (sensitivity) of Bcr-Abl
5) Confidence 0.49 Published 2008 Journal Drug design, development and therapy Section Body Doc Link PMC2761189 Disease Relevance 0 Pain Relevance 0.09
Other mechanisms of resistance to imatinib include alteration of the balance favoring the active state of ABL kinase, shifting the equilibrium between active and inactive states;15 a change in the conformation of the BCR-ABL protein, preventing imatinib from directly binding to its binding site;16 amplification of the BCR-ABL gene, leading to over-expression of BCR-ABL protein, as detected by FISH;13,16 or over-expression of the P-glycoprotein efflux pump, for which imatinib is the substrate.17,18 Additional mechanisms include the binding of the A1 acid glycoprotein (AGP) to imatinib in plasma, reducing its intracellular concentrations,19 or a less understood mechanism, the inhibition of ABCG2 protein functionality by imatinib.20
Positive_regulation (leading) of Gene_expression (expression) of BCR in plasma
6) Confidence 0.46 Published 2009 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2697539 Disease Relevance 0.21 Pain Relevance 0
This translocation fuses the genes encoding BCR and ABL, resulting in expression of the constitutively active protein tyrosine kinase, BCR-ABL.
Positive_regulation (resulting) of Gene_expression (expression) of BCR
7) Confidence 0.41 Published 2008 Journal OncoTargets and therapy Section Body Doc Link PMC2994207 Disease Relevance 1.46 Pain Relevance 0
Nilotinib has superior potency compared with imatinib as an inhibitor of BCR-ABL in vitro and in vivo: it is 10- to 30-fold more potent, as assessed by its ability to block proliferation of BCR-ABL dependent cell lines derived from CML patients (K562, Ku-812F) and cell lines (32D or Ba/F3) transfected to express the BCR-ABL protein (Figure 2; Weisberg et al 2005).
Positive_regulation (transfected) of Gene_expression (express) of BCR-ABL in 32D associated with myeloid leukemia and potency
8) Confidence 0.38 Published 2008 Journal OncoTargets and therapy Section Body Doc Link PMC2994207 Disease Relevance 0.16 Pain Relevance 0.08
This causes the production of the nonreceptor TK BCR┬ľABL fusion protein.
Positive_regulation (causes) of Gene_expression (production) of BCR
9) Confidence 0.15 Published 2006 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC1661649 Disease Relevance 0.73 Pain Relevance 0.04

General Comments

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