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Randomized Controlled Trial
. 2014 Nov;28(11):2251-4.
doi: 10.1038/leu.2014.206. Epub 2014 Jul 3.

Mitochondrial Priming of Chronic Lymphocytic Leukemia Patients Associates Bcl-xL Dependence With Alvocidib Response

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Free PMC article
Randomized Controlled Trial

Mitochondrial Priming of Chronic Lymphocytic Leukemia Patients Associates Bcl-xL Dependence With Alvocidib Response

W E Pierceall et al. Leukemia. .
Free PMC article

Conflict of interest statement

Conflict-of-interest disclosure

WEP, CD, RJL, NB, ME, and MHC are employees of Eutropics, Inc. SLW and DB are employees of Tolero Pharmaceuticals, Inc. The remaining authors declare no conflicts-of-interest. JCB and MRG are co-inventors of a patent pending for the use of alvocidib.

Figures

Figure 1
Figure 1. Bim and Hrk BH3 profiling of CLL patients are correlated with alvocidib response
A. Dot-plot depictions of the combined data set by stratification of response into 3 categories (PD, SD, PR). Note that increased priming trends are observed for both Bim(0.1) and Hrk from PD to SD and then from SD to PR. B. Dot-plot and ROC-plot depictions of Bim(0.1) and Hrk display response discrimination (2 groups: PD/SD, PR). C. Chromosome 12 trisomy multivariate analysis adds to Hrk prediction of CLL patient clinical response to alvocidib. While both Bim(0.1) and Hrk display AUC from ROC-plot depictions of 0.73, Hrk models benefit from inclusion of significant clinical adjustment variable trisomy12 to yield the increased AUC of 0.83 (p < .0001).
Figure 2
Figure 2. Bad peptide BH3 profiling correlates with TLS in CLL patients following treatment with alvocidib
A. Dot plot depictions indicate that higher Bad BH3 profiling readout values are significantly associated with the presence of TLS versus those patients who did not experience TLS. B. The Bad AUC from ROC-plot analysis was 0.75; this improved to 0.85 when combined with clinical adjustment variables age and ECOG status.

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