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- W2921195491 abstract "e18032 Background: Primarily monocyte-derived cytokines and soluble interleukin-2-receptor (sIL2R) form of a group of PIC which are significantly elevated in patients with CML-cp or CML-bc. C-reactive protein correlates to IL-6. IM is a tyrosine kinase inhibitor that blocks ATP binding site of kinase domain of Bcr/abl in CML. IM treatment with complete cytogenetic response but can acquire drug resistance via P-gp upregulation and lipid microdomains rich in sphingolipids and cholesterol of LR within plasma membranes important for regulating cell signaling and functions. Modulation of P-gp and disruption of LR/HDL-C upregulation readily overcame IM resistance. Methods: We present several cases of CML: CML-cp, CML-bc with evidence of resistance. After one year of IM therapy an 86 YOF with CML-cp developed Bcr/abl signaling c/w elevated PIC, sIL2R, CRP, acute coronary syndrome and low HDL-C (29.3 mg/dL). Results: Modulation of PIC and upregulation and increasing HDL-C by 50% with SV, IM dose adjustments and serial measurements of Bcr/abl ratio after two years, real time Bcr,abl ratio was ~ 5 log reduction, sIL2R normalized from 31,709.55 pg/ml to 5,345 pg/ml (Normal 1770-9753 pg/ml). CRP decreased by 30% and down to 6.23 mg/dL. Conclusions: IM an intracellular drug demonstrating high activity against Bcr,abl gene positive CML-cp or CML-bc patients may develop resistance by loss of cellular proliferation, upregulated P-gp and Bcr/abl protein with TK activity regulated signals of LR. Modulation of P-gp and disruption of LR/HDL-C upregulation with SV may synergistically allow intracellular levels of IM restoration of cytotoxicity and overcome resistance." @default.
- W2921195491 created "2019-03-22" @default.
- W2921195491 creator A5009606142 @default.
- W2921195491 date "2015-05-20" @default.
- W2921195491 modified "2023-09-26" @default.
- W2921195491 title "Modulation of lipid rafts (LR), p-glycoprotein (P-gp) and proinflammatory cytokines (PIC) with HMG-Co A reductase inhibitor simvastatin (SV) in chronic myelogenous leukemia (CML) patients with imatinib mesylate (IM) resistance." @default.
- W2921195491 doi "https://doi.org/10.1200/jco.2015.33.15_suppl.e18032" @default.
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