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. 2014 Jan;28(1):210-2.
doi: 10.1038/leu.2013.216. Epub 2013 Jul 17.

The Bcl-2 specific BH3 mimetic ABT-199: a promising targeted therapy for t(11;14) multiple myeloma

C Touzeau  1 , C Dousset  2 , S Le Gouill  3 , D Sampath  4 , J D Leverson  5 , A J Souers  5 , S Maïga  6 , M C Béné  7 , P Moreau  8 , C Pellat-Deceunynck  6 , M Amiot  6
Affiliations
Free PMC article

The Bcl-2 specific BH3 mimetic ABT-199: a promising targeted therapy for t(11;14) multiple myeloma

C Touzeau et al. Leukemia. 2014 Jan.
Free PMC article
No abstract available

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Figures

Figure 1
Figure 1
(a) Sensitivity to ABT-199 of HMCLs according to different molecular subgroups. (b) Sensitivity of HMCLs to ABT-199 compared to ABT-737. P-value was determined using Mann–Whitney test. For a and b, 25 HMCLs (respectively 8 CCND1 (KMS-12-PE, KMS-12-BM, SKMM-2, Karpas 620, U-266, XG-1, XG-5, NAN-7), 7 MAF (JJN-3, MM.1S, L-363, RPMI 8266, XG-6, BCN, NAN-1,) 7 MMSET (JIM-3, LP-1, OPM-2, NCI-H929, KMS-11, XG-7, NAN-3,) and 3 non recurrent translocation (XG-2, KMM-1, AMO1)) cell lines were cultured with increasing doses of ABT-199 or ABT-737 during 48 h. Cell death was assessed by APO 2.7 staining. LD50 was determined for each cell line. White symbols indicate wild-type P53 HMCL and black symbols indicate abnormal P53 HMCL (c) ABT-199 disrupts BH3-only/Bcl-2 heterodimers but not BH3-only/Bcl-xL heterodimers. Karpas 620 were treated or not for 6 h with 25 nM ABT-199. Lysate (600 μg) and immunoprecipitation were done as previously described using the indicated antibodies. The immunoprecipitates were analyzed for the presence of BH3-only. (d) The Bcl-2/Mcl-1 mRNA ratio discriminates cell lines sensitive or resistant to ABT-199. Quantitative PCR was performed using the following TaqMan probes (BCL2 (Hs00608023_m1), MCL1 (Hs00172036_m1) and RPL37a (Hs01102345_m1). The relative expression of Bcl-2 and Mcl-1 mRNA was calculated according to the equation of Pfaffl and normalized to JJN3 cell line. Sensitive HMCL were defined by a LD50 inferior to 100 nM. P-value was determined using Mann–Whitney test. (e) The LP-1 cell line was transfected with either si Control (Ct) or si Mcl-1. Following 48 h transfection, the protein level of Mcl-1 was assessed by immunoblotting, and cells were treated with ABT-199 for a further 48 h. Cell death was quantified by APO 2.7 staining. P-value was determined using paired Student's t-test. **P<0.008.
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References

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