OCT-1, ABCB1, and ABCG2 Expression in Imatinib-Resistant Chronic Myeloid Leukemia Treated with Dasatinib or Nilotinib
10.4068/cmj.2014.50.3.102
- Author:
Yeo Kyeoung KIM
1
;
Seung Shin LEE
;
Sung Hoon JEONG
;
Jae Sook AHN
;
Deok Hwan YANG
;
Je Jung LEE
;
Myung Geun SHIN
;
Hyeoung Joon KIM
Author Information
1. Department of Hematology-Oncology, Hematology Clinics, Chonnam National University Hwasun Hospital, Gwangju, Korea. yeokim@jnu.ac.kr
- Publication Type:Original Article
- Keywords:
ABCB1 protein;
ABCG2 protein;
Myeloid leukemia;
Imatinib
- MeSH:
Bone Marrow;
Cytogenetics;
Follow-Up Studies;
Hand;
Humans;
Leukemia, Myelogenous, Chronic, BCR-ABL Positive;
Leukemia, Myeloid;
Protein-Tyrosine Kinases;
RNA, Messenger;
Treatment Outcome;
Dasatinib;
Imatinib Mesylate
- From:Chonnam Medical Journal
2014;50(3):102-111
- CountryRepublic of Korea
- Language:English
-
Abstract:
This study explored drug transporter expression levels and their impact on clinical response to imatinib and second-generation tyrosine kinase inhibitors (TKIs) in imatinib- resistant chronic myeloid leukemia (CML). Imatinib-resistant chronic phase CML patients treated with dasatinib (n=10) and nilotinib (n=12) were enrolled. The mRNA expression of the OCT-1, ABCG2, and ABCB1 genes was quantified by using paired bone marrow samples obtained before administering imatinib and at the point of detecting imatinib resistance (just before starting second-generation TKIs). The expression levels of OCT-1 and ABCG2 were lower in follow-up than in imatinib-naive samples. ABCB1 revealed highly variable expression levels before and after imatinib treatment. In addition, median ABCB1 expression in follow-up samples was lower in patients achieving complete cytogenetic response or major molecular response during imatinib treatment than in failed patients. Higher ABCG2 expression in imatinib-exposed samples showed a negative impact on optimal response to dasatinib. Patients with higher ABCG2 expression in imatinib-exposed samples also had shorter progression- free survival with dasatinib treatment. However, no significant correlation was found between these drug transporter expression levels in imatinib-naive or imatinib- exposed samples and responses to nilotinib. In imatinib-resistant CML, OCT-1 and ABCG2 mRNA expression decreased after imatinib treatment. Patients with higher ABCG2 expression in imatinib-exposed samples showed poor treatment outcome with dasatinib. On the other hand, a higher expression level of ABCB1 in imatinib-exposed samples did not affect second-generation TKI responses but was correlated with poor imatinib responses.
