ABCB1 p.Glu255Lys
| Predicted by SNAP2: | A: D (80%), C: D (80%), D: D (53%), F: D (85%), G: D (85%), H: D (85%), I: D (85%), K: D (91%), L: D (85%), M: D (85%), N: D (80%), P: D (91%), Q: D (75%), R: D (91%), S: D (85%), T: D (85%), V: D (85%), W: D (91%), Y: D (85%), |
| Predicted by PROVEAN: | A: D, C: D, D: N, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: N, R: D, S: D, T: D, V: D, W: D, Y: D, |
[switch to compact view]
Comments [show]
None has been submitted yet.
[hide] Influence of CYP3A5 and drug transporter polymorph... J Hum Genet. 2010 Nov;55(11):731-7. Epub 2010 Aug 19. Takahashi N, Miura M, Scott SA, Kagaya H, Kameoka Y, Tagawa H, Saitoh H, Fujishima N, Yoshioka T, Hirokawa M, Sawada K
Influence of CYP3A5 and drug transporter polymorphisms on imatinib trough concentration and clinical response among patients with chronic phase chronic myeloid leukemia.
J Hum Genet. 2010 Nov;55(11):731-7. Epub 2010 Aug 19., [PMID:20720558]
Abstract [show]
Imatinib mesylate (IM) trough concentration varies among IM-treated chronic myeloid leukemia (CML) patients. Although IM pharmacokinetics is influenced by several enzymes and transporters, little is known about the role of pharmacogenetic variation in IM metabolism. In this study, associations between IM trough concentration, clinical response and 11 single-nucleotide polymorphisms in genes involved in IM pharmacokinetics (ABCB1, ABCC2, ABCG2 CYP3A5, SLC22A1 and SLCO1B3) were investigated among 67 Japanese chronic phase CML patients. IM trough concentration was significantly higher in patients with a major molecular response than in those without one (P=0.010). No significant correlations between IM trough concentration and age, weight, body mass index or biochemical data were observed. However, the dose-adjusted IM trough concentration was significantly higher in patients with ABCG2 421A than in those with 421C/C (P=0.015). By multivariate regression analysis, only ABCG2 421A was independently predictive of a higher dose-adjusted IM trough concentration (P=0.015). Moreover, previous studies have shown that the ABCG2 421C>A (p.Q141K) variant is prevalent among Japanese and Han Chinese individuals and less common among Africans and Caucasians. Together, these data indicate that plasma IM concentration monitoring and prospective ABCG2 421C>A genotyping may improve the efficacy of IM therapy, particularly among Asian CML patients.
Comments [show]
None has been submitted yet.
No. Sentence Comment
24 In patients without a CCyR, mutation analysis of the bcr-abl fusion transcript was performed using the Invader assay,31 which detects 25 mutations, including M244V, L248VR, G250E, Q252H, Q252R, Y253F, Y253H, E255K, E255V, E279K, F311L, T315A, T315I, F317L, M351T, F359IV, V379I, L387M, H396P, H396R, S417Y, E459K and F486S.
X
ABCB1 p.Glu255Lys 20720558:24:208
status: NEW[hide] Additive antileukemia effects by GFI1B- and BCR-AB... Cancer Gene Ther. 2013 Jul;20(7):421-7. doi: 10.1038/cgt.2013.31. Epub 2013 Jun 21. Koldehoff M, Zakrzewski JL, Beelen DW, Elmaagacli AH
Additive antileukemia effects by GFI1B- and BCR-ABL-specific siRNA in advanced phase chronic myeloid leukemic cells.
Cancer Gene Ther. 2013 Jul;20(7):421-7. doi: 10.1038/cgt.2013.31. Epub 2013 Jun 21., [PMID:23788109]
Abstract [show]
Previous studies demonstrated selective inhibition of the BCR-ABL (breakpoint cluster region-Abelson murine leukemia oncogene) tyrosine kinase by RNA interference in leukemic cells. In this study, we evaluated the effect of BCR-ABL small interfering RNA (siRNA) and GFI1B siRNA silencing on chronic myeloid leukemia (CML) cells in myeloid blast crises. The GFI1B gene was mapped to chromosome 9 and is, therefore, located downstream of the BCR-ABL translocation in CML cells. Co-transfection of BCR-ABL siRNA and GFI1B siRNA dramatically decreased cell viability and significantly induced apoptosis and inhibited proliferation in K562 cells (P<0.0001) and primary advanced phase CML cells (P<0.0001) versus controls. Furthermore, combining of BCR-ABL siRNA and GFI1B siRNA significantly modified the expression of several relevant genes including Myc, MDR1, MRP1 and tyrosyl-phosphoproteins in primary CML cells. Our data suggest that silencing of both BCR-ABL siRNA and GFI1B siRNA is associated with an additive antileukemic effect against K562 cells and primary advanced CML cells, further validating these genes as attractive therapeutic targets.
Comments [show]
None has been submitted yet.
No. Sentence Comment
92 Additive effects of co-transfection with BCR-ABL siRNA and GFI1B siRNA in primary CML cells In order to verify the above-described antileukemic effects, we assessed BCR-ABL siRNA and GFI1B siRNA transfection in primary cells obtained from four patients with BC of CML (patients with Y253F; F317L; and E255K mutation, and one patient with TKI resistant CML).
X
ABCB1 p.Glu255Lys 23788109:92:301
status: NEW