OCT-1, ABCB1, and ABCG2 Expression in Imatinib-Resistant Chronic Myeloid Leukemia Treated with Dasatinib or Nilotinib / 전남의대학술지
Chonnam Medical Journal
;
: 102-111, 2014.
Article
in English
| WPRIM
| ID: wpr-788294
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Bone Marrow
/
Protein-Tyrosine Kinases
/
RNA, Messenger
/
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
/
Leukemia, Myeloid
/
Follow-Up Studies
/
Treatment Outcome
/
Cytogenetics
/
Imatinib Mesylate
/
Dasatinib
Type of study:
Observational study
/
Prognostic study
Limits:
Humans
Language:
English
Journal:
Chonnam Medical Journal
Year:
2014
Type:
Article
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