In the polymorphism analysis, the 62 patients were divided into two groups, those with optimal response (32 individuals) and those with nonoptimal response (30 individuals). However, the frequencies of the genotypes at the studied loci were not different between the 2 response groups. Additional analysis looking at response to therapy with haplotypes had similar results.

Next, in the analysis of the RNA samples, the researchers selected 7 patients with optimal responses compared with 5 who had nonoptimal responses. Analysis of more than 34,000 genes revealed 26 differently expressed genes in patients with optimal compared with nonoptimal response (P <.05). 

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Among the identified molecular networks involved were glutathione metabolism, drug and xenobiotic metabolism, chemical mutagenesis, glycosaminoglycan degradation, and MAPK signaling pathway. However, these identified differences were small, and the researchers could not confirm them in qPCR analysis. 

In the miRNA analysis, the researchers compared 6 patients with optimal responses to 6 with nonoptimal responses, but found no difference in miRNA expression between the 2 groups.

“Apparently, efficacy of targeted therapy is determined not only by genetic factors, the environmental component of therapy response also plays a great role,” Dr Levrov and colleagues wrote. “It is necessary to continue [to] search for mechanisms of tumor cells sensitivity to therapy for their complete elimination.”

Reference

  1. Lavrov AV, Chelysheva EY, Adilgereeva EP, et al. Exome, transcriptome and miRNA analysis don’t reveal any molecular markers of TKI efficacy in primary CML patients. BMC Medical Genomics. 2019;12(Suppl 2):37.