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Lack of association between deletion polymorphism of BIM gene and in vitro drug sensitivity in B-cell precursor acute lymphoblastic leukemia.
- Source :
-
Leukemia research [Leuk Res] 2017 Sep; Vol. 60, pp. 24-30. Date of Electronic Publication: 2017 Jun 04. - Publication Year :
- 2017
-
Abstract
- A deletion polymorphism in the BIM gene was identified as an intrinsic mechanism for resistance to tyrosine kinase inhibitor in chronic myeloid leukemia patients in East Asia. BIM is also involved in the responses to glucocorticoid and chemotherapy in acute lymphoblastic leukemia (ALL), suggesting a possible association between deletion polymorphism of BIM and the chemosensitivity of ALL. Thus, we analyzed 72 B-cell precursor (BCP)-ALL cell lines established from Japanese patients. Indeed, higher BIM gene expression was associated with good in vitro sensitivities to glucocorticoid and chemotherapeutic agents used in induction therapy. We also analyzed the methylation status of the BIM gene promoter by next generation sequencing of genome bisulfite PCR products, since genetic polymorphism could be insignificant when epigenetically inactivated. Hypermethylation of the BIM gene promoter was associated with lower BIM gene expression and poorer sensitivity to vincristine. Of note, however, the prevalence of a deletion polymorphism was not associated with the BIM gene expression level or drug sensitivities in BCP-ALL cell lines, in which the BIM gene was unmethylated. These observations suggest that an association of a deletion polymorphism of BIM and the response to induction therapy in BCP-ALL may be clinically minimal.<br /> (Copyright © 2017. Published by Elsevier Ltd.)
- Subjects :
- Antineoplastic Agents pharmacology
Asian People
Bcl-2-Like Protein 11 physiology
Cell Line, Tumor
DNA Methylation
Glucocorticoids pharmacology
Humans
Polymorphism, Genetic
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma pathology
Promoter Regions, Genetic
Vincristine pharmacology
Bcl-2-Like Protein 11 genetics
Drug Resistance, Neoplasm genetics
Gene Deletion
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1873-5835
- Volume :
- 60
- Database :
- MEDLINE
- Journal :
- Leukemia research
- Publication Type :
- Academic Journal
- Accession number :
- 28641145
- Full Text :
- https://doi.org/10.1016/j.leukres.2017.06.003