Imatinib and chronic myeloid leukemia (WP3640)
Homo sapiens
Hematopoietic Stem Cells found in bone marrow can differentiate into Monocytes and Erythrocytes, or in the case of Chronic Myeloid Leukemia (CML), they can continue to proliferate, undifferentiated, in blood. CML is caused by the Philadelphia translocation (Ph), which puts ABL behind BCR. The BRC-ABL fusion is a constitutively on tyrosine kinase that indirectly counteracts erythroid differentiation, thus promoting the continued proliferation underlying CML. Imatinib is a tyrosine kinase inhibitor that binds ABL and in turn promotes healthy erythroid differentiation by counteracting BRC-ABL activity. Imatinib resistance can be conferred by the over-expression of ABC drug transporters and competitive binding kinases. The pathway diagram above aligns molecules with the cell fates they promote, to help keep track of inhibition-of-inhibition-of-inhibition sequences, for example. The known mechanisms of imatinib resistance are at the bottom, under CML cell fate and are shown interacting with imatinib, which is under the erythrocyte cell fate. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP3640 CPTAC Assay Portal]
Authors
Alex Pico , Kristina Hanspers , Eric Weitz , and Egon WillighagenActivity
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Cited In
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Organisms
Homo sapiensCommunities
CPTACAnnotations
Disease Ontology
chronic myeloid leukemiaCell Type Ontology
hematopoietic stem cell erythrocyte myeloid leukocytePathway Ontology
disease pathway chronic myeloid leukemia pathwayLabel | Type | Compact URI | Comment |
---|---|---|---|
Imatinib | Metabolite | hmdb:HMDB0014757 | |
BCR | GeneProduct | ensembl:ENSG00000186716 | |
ABL1 | GeneProduct | ensembl:ENSG00000097007 | |
MYC | GeneProduct | ensembl:ENSG00000136997 | |
ABCB1 | GeneProduct | ensembl:ENSG00000085563 | |
ABCG2 | GeneProduct | ensembl:ENSG00000118777 | |
KIT | GeneProduct | ensembl:ENSG00000157404 | |
PDGFRA | GeneProduct | ensembl:ENSG00000134853 | |
PDGFRB | GeneProduct | ensembl:ENSG00000113721 | |
CDKN1B | GeneProduct | ensembl:ENSG00000111276 | |
SKP2 | GeneProduct | ensembl:ENSG00000145604 | |
CSF1R | GeneProduct | ensembl:ENSG00000182578 | |
GADD45A | GeneProduct | ensembl:ENSG00000116717 | |
FOXO3 | GeneProduct | ensembl:ENSG00000118689 | |
NOP2 | GeneProduct | ensembl:ENSG00000111641 | |
SPRED2 | GeneProduct | ensembl:ENSG00000198369 | |
LYL1 | GeneProduct | ensembl:ENSG00000104903 | |
PIM1 | GeneProduct | ensembl:ENSG00000137193 | |
PIM2 | GeneProduct | ensembl:ENSG00000102096 | |
GAB2 | GeneProduct | ensembl:ENSG00000033327 | |
FLT1 | GeneProduct | ensembl:ENSG00000102755 |
References
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