Overexpression of P-glycoprotein and resistance to Imatinib in chronic myeloid leukemia patients.
ATP Binding Cassette Transporter, Subfamily B, Member 1
/ metabolism
Antineoplastic Agents
/ pharmacology
Biomarkers, Tumor
/ metabolism
Case-Control Studies
Drug Resistance, Neoplasm
Female
Follow-Up Studies
Humans
Imatinib Mesylate
/ pharmacology
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
/ drug therapy
Male
Middle Aged
Prognosis
Retrospective Studies
Survival Rate
Imatinib
P-glycoprotein
chronic myeloid leukemia
multidrug resistance
resistance
Journal
Journal of clinical laboratory analysis
ISSN: 1098-2825
Titre abrégé: J Clin Lab Anal
Pays: United States
ID NLM: 8801384
Informations de publication
Date de publication:
Sep 2020
Sep 2020
Historique:
received:
30
01
2020
revised:
07
04
2020
accepted:
20
04
2020
pubmed:
28
7
2020
medline:
15
7
2021
entrez:
28
7
2020
Statut:
ppublish
Résumé
The P-glycoprotein (P-gp) is one of the mechanisms of Imatinib (IM) resistance in chronic myeloid leukemia (CML). P-gp has been identified as an efflux pump involved in releasing of IM outside CML cells. To date, the P-gp involvement in the IM resistance development was not completely understood. Therefore, the present study aimed at measuring the P-gp expression level on lymphocytes from Tunisian patients with CML and correlating this level with a molecular response to IM. The expression of P-gp on peripheral blood lymphocytes from 59 Tunisian patients with CML (27 IM responder patients vs 32 IM non-responder patients) was evaluated by flow cytometry. Our finding showed significantly positive expression of P-gp in the lymphocytes from the IM non-responder group when compared to the IM-responder group (P = .001). In IM non-responder CML patients, the comparison between CCyR achievers and non-achievers showed a high mean fluorescence intensity (MFI) of P-gp expression in patients who did not achieve their CCyR (P = .001). The comparison between patients with primary and secondary resistance to IM showed an increasing MFI value in patients with primary resistance to IM (P = .001). Besides, the comparison between nilotinib-treated and dasatinib-treated patients proved a high value of MFI in nilotinib-treated patients (P = .001). The overexpression of P-gp on lymphocytes has significantly correlated with the failed molecular response to IM in patients with CML.
Sections du résumé
BACKGROUND
BACKGROUND
The P-glycoprotein (P-gp) is one of the mechanisms of Imatinib (IM) resistance in chronic myeloid leukemia (CML). P-gp has been identified as an efflux pump involved in releasing of IM outside CML cells. To date, the P-gp involvement in the IM resistance development was not completely understood. Therefore, the present study aimed at measuring the P-gp expression level on lymphocytes from Tunisian patients with CML and correlating this level with a molecular response to IM.
METHOD
METHODS
The expression of P-gp on peripheral blood lymphocytes from 59 Tunisian patients with CML (27 IM responder patients vs 32 IM non-responder patients) was evaluated by flow cytometry.
RESULT
RESULTS
Our finding showed significantly positive expression of P-gp in the lymphocytes from the IM non-responder group when compared to the IM-responder group (P = .001). In IM non-responder CML patients, the comparison between CCyR achievers and non-achievers showed a high mean fluorescence intensity (MFI) of P-gp expression in patients who did not achieve their CCyR (P = .001). The comparison between patients with primary and secondary resistance to IM showed an increasing MFI value in patients with primary resistance to IM (P = .001). Besides, the comparison between nilotinib-treated and dasatinib-treated patients proved a high value of MFI in nilotinib-treated patients (P = .001).
CONCLUSION
CONCLUSIONS
The overexpression of P-gp on lymphocytes has significantly correlated with the failed molecular response to IM in patients with CML.
Identifiants
pubmed: 32715517
doi: 10.1002/jcla.23374
pmc: PMC7521244
doi:
Substances chimiques
ATP Binding Cassette Transporter, Subfamily B, Member 1
0
Antineoplastic Agents
0
Biomarkers, Tumor
0
Imatinib Mesylate
8A1O1M485B
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e23374Informations de copyright
© 2020 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.
Références
Blood. 2003 Dec 15;102(13):4499-503
pubmed: 12881321
Haematologica. 2014 Sep;99(9):1441-7
pubmed: 24837466
Clin Cancer Res. 2003 Feb;9(2):625-32
pubmed: 12576428
Neoplasia. 2010 Aug;12(8):628-36
pubmed: 20689757
Cancer. 2011 Mar 15;117(6):1113-22
pubmed: 20960522
Hematology Am Soc Hematol Educ Program. 2009;:461-76
pubmed: 20008232
Pharmgenomics Pers Med. 2013 Aug 20;6:63-72
pubmed: 24019750
PLoS One. 2010 Oct 08;5(10):e13186
pubmed: 20949032
Leukemia. 2016 Aug;30(8):1648-71
pubmed: 27121688
Blood. 2011 Sep 29;118(13):3634-44
pubmed: 21821701
Blood. 2004 Dec 1;104(12):3739-45
pubmed: 15315971
Leukemia. 2013 Jan;27(1):107-12
pubmed: 22763385
J Pharmacol Exp Ther. 2002 Sep;302(3):963-71
pubmed: 12183653
Ann Intern Med. 1999 Aug 3;131(3):207-19
pubmed: 10428738
J Clin Lab Anal. 2020 Sep;34(9):e23374
pubmed: 32715517
Leukemia. 2004 Mar;18(3):401-8
pubmed: 14724652
Leuk Res. 2003 Mar;27(3):243-51
pubmed: 12537977
Leukemia. 2005 Sep;19(9):1590-6
pubmed: 16001089
Pharmacol Ther. 2015 May;149:1-123
pubmed: 25435018
Blood. 2002 Mar 15;99(6):1928-37
pubmed: 11877262
Cancer Control. 2009 Apr;16(2):122-31
pubmed: 19337198
Leuk Res. 2007 Apr;31(4):445-54
pubmed: 16979236
Biochim Biophys Acta. 2013 May;1832(5):606-17
pubmed: 23376112
Leuk Res. 2015 Oct;39(10):1109-16
pubmed: 26248945
Cancer Chemother Pharmacol. 2017 Apr;79(4):737-745
pubmed: 28286932
Ann Oncol. 2006 Sep;17 Suppl 10:x274-9
pubmed: 17018738
Cytometry B Clin Cytom. 2004 Sep;61(1):1-8
pubmed: 15351976
Blood. 2003 Mar 15;101(6):2368-73
pubmed: 12609962
Molecules. 2018 Jan 07;23(1):
pubmed: 29316665
Blood. 1984 Apr;63(4):789-99
pubmed: 6584184
Crit Rev Oncol Hematol. 2006 Feb;57(2):145-64
pubmed: 16213151
Chin J Cancer. 2012 Feb;31(2):110-8
pubmed: 22098951
PLoS One. 2016 Aug 18;11(8):e0161470
pubmed: 27536777
J Biol Chem. 2010 Mar 5;285(10):7575-86
pubmed: 20061384
Eur J Pharm Sci. 2006 Jul;28(4):300-6
pubmed: 16707254
Leuk Res Treatment. 2012;2012:671702
pubmed: 23259070
Am J Hematol. 2016 Feb;91(2):252-65
pubmed: 26799612
Exp Cell Res. 1989 Dec;185(2):496-505
pubmed: 2480910