NDLI: ABCB1 haplotypes are associated with P-gp activity and affect a major molecular response in chronic myeloid leukemia patients treated with a standard dose of imatinib

Content Provider	PubMed Central
Author	Vivona, Douglas Lima, Luciene Terezina Rodrigues, Alice Cristina Bueno, Carolina Tosin Alcantara, Greyce Kelly Steinhorst Barros, Luiza Saldanha Ribeiro Hungria, Vania Tiestsche De Moraes Chiattone, Carlos SÉrgio De, Lours Lopes Ferrari Chauffaille Maria Maria, Guerra-shinohara Elvira
Copyright Year	2014
Abstract	Despite the high efficacy of imatinib mesylate (IM) treatment for chronic myeloid leukemia (CML) patients, some individuals develop resistance due to impaired bioavailability. It has been previously demonstrated that the haplotypes for ATP-binding cassette subfamily B member 1 (ABCB1)with c.1236C>T, c.3435C>T and c.2677G>T/A polymorphisms markedly affect the secondary structure of ABCB1 mRNA and its activity. These modifications may affect efflux transporter activity and response to treatment with IM. The aim of the present study was to investigate the influence of ABCB1 haplotypes on P-glycoprotein (P-gp) activity, IM plasma levels and IM response. In total, 28 chronic-phase CML patients treated with a standard dose of IM (400 mg/day) were studied. The patients were selected according to the haplotypes of ABCB1, with c.1236C>T, c.3435C>T and c.2677G>T polymorphisms, and were classified into two groups based on the presence of the mutated allele in each genotype for the three ABCB1 polymorphisms. In addition, expression of P-gp and breakpoint cluster region-abelson 1 (BCR-ABL1), ABCB1 and solute carrier family 22 member 1 (SLC22A1) mRNA were evaluated. The P-gp activity in the wild-type group was found to be higher than that in the mutated group (59.1 vs. 38.3%; P=0.001). Furthermore, the patients who did not achieve major molecular response (MMR) showed a higher rate of efflux mediated by P-gp when compared with individuals who achieved MMR (64.7 vs. 45.7%; P=0.001). All patients without MMR demonstrated effluxes of >60%. In addition, patients without MMR exhibited lower plasma concentrations of IM compared with those with MMR (0.51 vs. 1.42 μg/ml; P=0.001). Higher levels of SLC22A1 mRNA were observed in patients who achieved MMR and complete molecular response (P<0.05). In conclusion, the ABCB1 1236CT/3435CT/2677GT and 1236TT/3435TT/2677TT haplotypes are associated with reduced P-gp activity and MMR in chronic-phase CML patients treated with a standard dose of IM.
Related Links	http://dx.doi.org/10.3892/ol.2014.1857
Starting Page	1313
File Format	PDF
ISSN	17921074
e-ISSN	17921082
Journal	Oncology Letters
Issue Number	4
Volume Number	7
Language	English
Publisher	D.A. Spandidos
Publisher Date	2014-02-01
Access Restriction	Open
Rights Holder	D.A. Spandidos
Subject Keyword	Cancer Research Oncology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

ABCB1 haplotype is associated with major molecular response in chronic myeloid leukemia patients treated with standard-dose of imatinib.

Imatinib Optimized Therapy Improves Major Molecular Response Rates in Patients with Chronic Myeloid Leukemia

Clinical Relevance of ABCB1, ABCG2, and ABCC2 Gene Polymorphisms in Chronic Myeloid Leukemia Patients Treated With Nilotinib

CYP3A activity influences imatinib response in patients with chronic myeloid leukemia: a pilot study on in vivo CYP3A activity

Multicenter Independent Assessment of Outcomes in Chronic Myeloid Leukemia Patients Treated With Imatinib

MicroRNA expression profiling in Imatinib-resistant Chronic Myeloid Leukemia patients without clinically significant ABL1-mutations

Telomere length shortening is associated with treatment-free remission in chronic myeloid leukemia patients

Dasatinib-associated major molecular responses in patients with chronic myeloid leukemia in chronic phase following imatinib failure: response dynamics and predictive value

Efficacy of Imatinib Dose Escalation in Patients With Chronic Myeloid Leukemia in Chronic Phase

ABCB1 haplotypes are associated with P-gp activity and affect a major molecular response in chronic myeloid leukemia patients treated with a standard dose of imatinib

Similar Documents

ABCB1 haplotype is associated with major molecular response in chronic myeloid leukemia patients treated with standard-dose of imatinib.

Imatinib Optimized Therapy Improves Major Molecular Response Rates in Patients with Chronic Myeloid Leukemia

Clinical Relevance of ABCB1, ABCG2, and ABCC2 Gene Polymorphisms in Chronic Myeloid Leukemia Patients Treated With Nilotinib

CYP3A activity influences imatinib response in patients with chronic myeloid leukemia: a pilot study on in vivo CYP3A activity

Multicenter Independent Assessment of Outcomes in Chronic Myeloid Leukemia Patients Treated With Imatinib

MicroRNA expression profiling in Imatinib-resistant Chronic Myeloid Leukemia patients without clinically significant ABL1-mutations

Telomere length shortening is associated with treatment-free remission in chronic myeloid leukemia patients

Dasatinib-associated major molecular responses in patients with chronic myeloid leukemia in chronic phase following imatinib failure: response dynamics and predictive value

Efficacy of Imatinib Dose Escalation in Patients With Chronic Myeloid Leukemia in Chronic Phase

ABCB1 haplotypes are associated with P-gp activity and affect a major molecular response in chronic myeloid leukemia patients treated with a standard dose of imatinib