Detection of BIM (BCL2L11) Polymorphic Variants in Chronic Myeloid Leukemia by Q-Invader Assay and Their Clinical Significance - Abstract
Background: Accumulating evidence suggests that genetic variants, including deletion and single nucleotide polymorphism (SNP) have role in the genesis and progression of various cancers. BIM (also known as BCL2L11) is a proapoptotic protein that is essential in the tyrosine kinase inhibitor (TKI)-induced apoptosis in chronic myeloid leukemia (CML) cells. We therefore attempted to develop new detection assay system of the BIM genetic variants in CML patients and clinical relevance.
Subjects and methods: We assessed knownBIM polymorphic variants (BIMdeletion polymorphism in intron 2 and silent SNP in BIM exon 5) by using the Q-Invader method with molecular response by TKIs in 47 Japanese chronic myeloid leukemia (CML) patients who achieved 4-log reduction of molecular response (MR4.0) or more.
Results: The Q-Invader assay was able to detect BIM deletion polymorphism expanding approximately 2900 bp and BIMSNP at exon 5 (c465C>T). Six of 47 (12.8%) showed the BIM intron 2 deletion polymorphism and 11 of 47 (23.4%) CML patients did the SNP. In healthy volunteers, 4 of 20 (20%) had the BIM deletion polymorphism and 4 of 20 (20%) did the BIM SNP: none of our subjects had the
BIM deletion polymorphism and SNP (c465C>T) concurrently. CML patients with BIMpolymorphic variants showed high frequencies of reduction of imatinib dose and switching to second-line
Conclusion: TKIs. BIM is an essential protein for the apoptotic process in cancer cells with TKI therapy, the detection assay of polymorphic variants, such as Q-Invader assay, could be useful in clinical practice.