The clinical significance of ABCB1 overexpression in predicting outcome of CML patients undergoing first-line imatinib treatment

Tyrosine kinase inhibitor (TKI) therapy results in excellent responses in the majority of patients with chronic myeloid leukaemia. First-line imatinib treatment, with selective switching to nilotinib when patients fail to meet specific molecular targets or for imatinib intolerance, results in excell...

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Bibliographic Details
Published in:Leukemia 2017-01, Vol.31 (1), p.75-82
Main Authors: Eadie, L N, Dang, P, Saunders, V A, Yeung, D T, Osborn, M P, Grigg, A P, Hughes, T P, White, D L
Format: Article
Language:English
Subjects:
ATP Binding Cassette Transporter, Sub-Family B - analysis
ATP Binding Cassette Transporter, Sub-Family B - genetics
Blast crisis
Cells, Cultured
Chronic myeloid leukemia
Clinical significance
Dosage and administration
Drug Resistance, Neoplasm
Drug therapy
Early experience
Efflux
Enzyme inhibitors
Gene Expression
Genetic aspects
Humans
Imatinib
Imatinib mesylate
Imatinib Mesylate - pharmacology
Imatinib Mesylate - therapeutic use
Inhibitor drugs
Intolerance
Kinases
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - diagnosis
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy
Medical research
Mutation
Patients
Predictive Value of Tests
Prognosis
Protein Kinase Inhibitors - pharmacology
Protein-tyrosine kinase
RNA, Messenger - analysis
Software
Therapy
Tyrosine
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Summary:Tyrosine kinase inhibitor (TKI) therapy results in excellent responses in the majority of patients with chronic myeloid leukaemia. First-line imatinib treatment, with selective switching to nilotinib when patients fail to meet specific molecular targets or for imatinib intolerance, results in excellent overall molecular responses and survival. However, this strategy is less effective in cases of primary imatinib resistance; moreover, 25% of patients develop secondary resistance such that 20-35% of patients initially treated with imatinib will eventually experience treatment failure. Early identification of these patients is of high clinical relevance. Since the drug efflux transporter ABCB1 has previously been implicated in TKI resistance, we determined if early increases in ABCB1 mRNA expression (fold change from diagnosis to day 22 of imatinib therapy) predict for patient response. Indeed, patients exhibiting a high fold rise (⩾2.2, n=79) were significantly less likely to achieve early molecular response (BCR-ABL1 ⩽10% at 3 months; P=0.001), major molecular response (P
ISSN:0887-6924
1476-5551
DOI:10.1038/leu.2016.179