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INVESTIGATION OF POLYMORPHISMS RELATED TO MIR-608 IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA
Author(s):
Naira Ryabchikova
,
Naira Ryabchikova
Affiliations:
Bashkir State Medical University,UFA,Russian Federation
Guzel Safuanova
,
Guzel Safuanova
Affiliations:
Bashkir State Medical University,UFA,Russian Federation
Ildar Minniakhmetov
,
Ildar Minniakhmetov
Affiliations:
IBG USC RAS,UFA,Russian Federation
Aleksandr Sultanbaev
,
Aleksandr Sultanbaev
Affiliations:
Bashkir State Medical University,UFA,Russian Federation
Elza Khusnutdinova
Elza Khusnutdinova
Affiliations:
IBG USC RAS,UFA,Russian Federation
(Abstract release date: 05/18/17) EHA Library. Minniakhmetov I. 05/18/17; 182517; PB1803
Ildar Minniakhmetov
Ildar Minniakhmetov
Contributions
PDF Abstract
Abstract

Abstract: PB1803

Type: Publication Only

Background

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the expression of the BCR-ABL oncoprotein, which is essential for the pathogenesis of the disease. Imatinib, an ATP-competitive selective inhibitor of BCR-ABL, has unprecedented efficacy for the treatment of CML. Several cellular and genetic mechanisms of imatinib resistance have been proposed, including overexpression of the BCR-ABL gene, the tyrosine kinase domain mutations, pharmacokinetic and pharmacodynamic factors.

Aims
The purpose of this study was to investigate miRNA-608 role in response to therapy with tyrosine kinase inhibitors (Imatinib). In this study, we analyzed rs9762 SNP located in a miRNA-608 binding site of 3′UTR of BCR-ABL gene and rs4919510 SNP in the mature sequence of miR-608 in CML patients with different response to tyrosine kinase inhibitor therapy. These polymorphisms disrupt the negative effect of mir-608 on its target BCR-ABL.

Methods

In our study 76 CML patients at the age of 15−65 were involved. Genomic DNA was extracted from peripheral blood leukocytes by standard phenol-chloroform method. Genotyping was performed by the PCR-RFLP technique.

Results

Combination of genotypes affecting mir-608/BCR-ABL1 interaction (*GG in mir-608 binding site and/or *GG in mature miRNA itself) was revealed with 81% in CML patients with uneffective therapy. We suggest that mir-608 could possess oncosuppressing activity as mir-203 but it should be confirmed by further experiments.

Conclusion
miRNAs could be a perspective tool for therapy and polymorphisms affecting its regulation should also be considered.

Session topic: 7. Chronic myeloid leukemia - Biology

Keyword(s): Polymorphism, Imatinib resistance, Chronic myeloid leukemia

Abstract: PB1803

Type: Publication Only

Background

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the expression of the BCR-ABL oncoprotein, which is essential for the pathogenesis of the disease. Imatinib, an ATP-competitive selective inhibitor of BCR-ABL, has unprecedented efficacy for the treatment of CML. Several cellular and genetic mechanisms of imatinib resistance have been proposed, including overexpression of the BCR-ABL gene, the tyrosine kinase domain mutations, pharmacokinetic and pharmacodynamic factors.

Aims
The purpose of this study was to investigate miRNA-608 role in response to therapy with tyrosine kinase inhibitors (Imatinib). In this study, we analyzed rs9762 SNP located in a miRNA-608 binding site of 3′UTR of BCR-ABL gene and rs4919510 SNP in the mature sequence of miR-608 in CML patients with different response to tyrosine kinase inhibitor therapy. These polymorphisms disrupt the negative effect of mir-608 on its target BCR-ABL.

Methods

In our study 76 CML patients at the age of 15−65 were involved. Genomic DNA was extracted from peripheral blood leukocytes by standard phenol-chloroform method. Genotyping was performed by the PCR-RFLP technique.

Results

Combination of genotypes affecting mir-608/BCR-ABL1 interaction (*GG in mir-608 binding site and/or *GG in mature miRNA itself) was revealed with 81% in CML patients with uneffective therapy. We suggest that mir-608 could possess oncosuppressing activity as mir-203 but it should be confirmed by further experiments.

Conclusion
miRNAs could be a perspective tool for therapy and polymorphisms affecting its regulation should also be considered.

Session topic: 7. Chronic myeloid leukemia - Biology

Keyword(s): Polymorphism, Imatinib resistance, Chronic myeloid leukemia

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