INT239412

Context Info Confidence 0.28 First Reported 2008 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 8 Total Number 8 Disease Relevance 5.39 Pain Relevance 0.18

cytosol (ABL1) protein modification process (ABL1) mitochondrion (ABL1) nucleolus (ABL1) nucleus (ABL1) DNA binding (ABL1)

Anatomy Link Frequency plasma 1 ABL1 (Homo sapiens)

Pain Link Frequency Relevance Heat adenocard 1 99.72 Potency 4 88.60 rheumatoid arthritis 1 87.92 Pain 16 37.48 cytokine 20 5.00 headache 17 5.00 pruritus 8 5.00 corticosteroid 3 5.00 Spinal cord 3 5.00 Paresthesia 3 5.00

Disease Link Frequency Relevance Heat Disease 108 98.56 Congenital Anomalies 35 98.24 Hypolipidemia 33 97.62 Ophthalmoplegia 3 96.40 Myeloid Leukemia 122 95.48 Anisocoria 3 95.04 Ocular Toxicity (including Many Sub-types) 30 94.08 Strabismus 3 93.20 Gastrointestinal Stromal Tumor 104 92.32 Neuropathic Pain 18 92.12

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Although there are multiple mechanisms involved in the emergence of resistance, usually resistance develops because of a mutation in the adenosine triphosphate-binding pocket of the BCR-ABL1 oncoprotein, which makes imatinib binding impossible.

BCR-ABL1 oncoprotein Binding (binding) of associated with adenocard

1) Confidence 0.28 Published 2010 Journal BMC Blood Disord Section Body Doc Link PMC3017013 Disease Relevance 0.22 Pain Relevance 0.05

At age 11, routine blood tests revealed acanthocytosis with undetectable plasma cholesterol and triglyceride, which together with normal parental lipid profiles suggested a diagnosis of ABL.

ABL Binding (diagnosis) of in plasma associated with hypolipidemia

2) Confidence 0.26 Published 2008 Journal Orphanet J Rare Dis Section Body Doc Link PMC2467409 Disease Relevance 0.54 Pain Relevance 0

Furthermore, anecdotal evidence, such as the history of the two patients reported here, suggests that vitamin replacement treatment can reduce morbidity and delay early mortality associated with ABL.

ABL Binding (associated) of

3) Confidence 0.25 Published 2008 Journal Orphanet J Rare Dis Section Body Doc Link PMC2467409 Disease Relevance 0.41 Pain Relevance 0

Of note, all ABL patients who received vitamin therapy prior to 2 years of age were free of the neurologic and systemic complications that are usually associated with untreated ABL [17].

ABL Binding (associated) of

4) Confidence 0.25 Published 2008 Journal Orphanet J Rare Dis Section Body Doc Link PMC2467409 Disease Relevance 1.40 Pain Relevance 0

The first of these disease-tailored products has been imatinib mesylate (IM) which blocks the ATP-binding pocket on the BCR-ABL tyrosine-kinase and thus prevents the activation of this enzyme which plays the key role in the pathogenesis of CML [13].

BCR-ABL Binding (binding) of associated with myeloid leukemia and disease

5) Confidence 0.15 Published 2010 Journal Clinical and Developmental Immunology Section Body Doc Link PMC3004381 Disease Relevance 1.18 Pain Relevance 0.04

Bosutinib binds to an intermediate form of BCR-ABL [8].

BCR-ABL Binding (binds) of

6) Confidence 0.07 Published 2010 Journal J Hematol Oncol Section Body Doc Link PMC3000369 Disease Relevance 0.38 Pain Relevance 0.04

Dasatinib has a completely different chemical structure to imatinib and, unlike imatinib and nilotinib, binds BCR-ABL in the active conformation [10,11].

BCR-ABL Binding (binds) of

7) Confidence 0.07 Published 2010 Journal J Hematol Oncol Section Body Doc Link PMC3000369 Disease Relevance 0.36 Pain Relevance 0.04

Imatinib is a selective tyrosine kinase inhibitor which binds KIT, Bcr-Abl, PDGFA/PDGFB.

Bcr-Abl Binding (binds) of

8) Confidence 0.04 Published 2010 Journal Biologics : Targets & Therapy Section Body Doc Link PMC2819895 Disease Relevance 0.91 Pain Relevance 0

General Comments

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