Imatinib and chronic myeloid leukemia (Homo sapiens)
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Description
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.
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- Amente S, Zhang J, Lavadera ML, Lania L, Avvedimento EV, Majello B; ''Myc and PI3K/AKT signaling cooperatively repress FOXO3a-dependent PUMA and GADD45a gene expression.''; Nucleic Acids Res, 2011 PubMed Europe PMC Scholia
- Gómez-Casares MT, García-Alegria E, López-Jorge CE, Ferrándiz N, Blanco R, Alvarez S, Vaqué JP, Bretones G, Caraballo JM, Sánchez-Bailón P, Delgado MD, Martín-Perez J, Cigudosa JC, León J; ''MYC antagonizes the differentiation induced by imatinib in chronic myeloid leukemia cells through downregulation of p27(KIP1.).''; Oncogene, 2013 PubMed Europe PMC Scholia
- Scheinfeld N; ''A comprehensive review of imatinib mesylate (Gleevec) for dermatological diseases.''; J Drugs Dermatol, 2006 PubMed Europe PMC Scholia
- Eechoute K, Sparreboom A, Burger H, Franke RM, Schiavon G, Verweij J, Loos WJ, Wiemer EA, Mathijssen RH; ''Drug transporters and imatinib treatment: implications for clinical practice.''; Clin Cancer Res, 2011 PubMed Europe PMC Scholia
- Daub H, Specht K, Ullrich A; ''Strategies to overcome resistance to targeted protein kinase inhibitors.''; Nat Rev Drug Discov, 2004 PubMed Europe PMC Scholia
- Andreu EJ, Lledó E, Poch E, Ivorra C, Albero MP, Martínez-Climent JA, Montiel-Duarte C, Rifón J, Pérez-Calvo J, Arbona C, Prósper F, Pérez-Roger I; ''BCR-ABL induces the expression of Skp2 through the PI3K pathway to promote p27Kip1 degradation and proliferation of chronic myelogenous leukemia cells.''; Cancer Res, 2005 PubMed Europe PMC Scholia
- Colombo T, Farina L, Macino G, Paci P; ''PVT1: a rising star among oncogenic long noncoding RNAs.''; Biomed Res Int, 2015 PubMed Europe PMC Scholia
- Carramusa L, Contino F, Ferro A, Minafra L, Perconti G, Giallongo A, Feo S; ''The PVT-1 oncogene is a Myc protein target that is overexpressed in transformed cells.''; J Cell Physiol, 2007 PubMed Europe PMC Scholia
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