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Added: (Wed Oct 10 2018)
Pressbox (Press Release) - , San Diego, CA, http://www.graphpad.com). Results were expressed as the average IC50 calculated from three different primary samples. For CFC assays, primary samples were treated Nutlin3a with FAK or ��-catenin inhibitors and then plated in Methocult H4435 in duplicate. Colonies were counted 18 days after seeding. Results are expressed as average CFC output from three different primary samples. A total of 5�C10 individual CFC-derived colonies were analyzed cytogenetically to confirm their leukemic origin. Results were based in each case on an examination of at least two Giemsa-banded metaphases per individually processed CFC-derived colony. Pairwise comparisons between continuous variable distributions were carried out with the Kruskal�CWallis test and Fisher's Dactolisib molecular weight exact test for categorical variables. The mean �� SEM was calculated for each group. Kaplan�CMeier curves were plotted for OS, EFS, and length of clinical remission (LCR) and compared using the Mantel-Cox log-rank test. OS endpoints, measured from time of diagnosis, were death (failure) or survival at the last follow-up (censored). EFS endpoints, measured from time of diagnosis, were death or relapse (failure) and survival at the last follow-up (censored). LCR endpoints, measured from time of complete remission, were death or relapse (failure) and survival at the last follow-up (censored). Results were significant at p <.05. A new survey of cells from 48 cases of AML showed that 52% of these samples expressed FAK (Supporting Information Table S1), a percentage close to that reported in our previous study . Further analysis of FAK isoform expression in the 48 samples analyzed here led to their stratification into three groups: a FAK? group, a FAK0 group (positive only for FAK0 isoforms), and a FAK6* group (positive for FAK6 and/or FAK6, 7 and/or FAK6, 28 isoforms) based on the main isoforms detected (Table 1; Supporting Information Table S1). The groups of AML patients thus identified did not show any differences in age at diagnosis, sex distribution, presence or absence of a FLT3-internal tandem duplication (ITD) mutation or cytogenetic risk factors. However, expression of FAK6* variants was associated with a decreased OS, EFS, and length of clinical remission as compared to MK0683 concentration FAK? cases (Fig. 1). The FAK6* group also showed an increased death rate (even in under 60-year-old patients, Supporting Information Table S1) and early death (i.e., death before a first complete remission was achieved, Table 1). Altogether, these data show that FAK6* variant expression in the blasts from AML patients is independently associated with a poor outcome, whereas expression of FAK proteins that do not include contributions from alternative exons (FAK0 proteins) had no significant prognostic impact.Submitted by: