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3. MDR1 expression predicts outcome of Ph+ chronic phase CML patients on second-line nilotinib therapy after imatinib failure

Author

Dominik Wolf, Purkayastha D, Martin C. Müller, Richard C. Woodman, Mridul Agrawal, Alice Fabarius, Susanne Saussele, Andreas Hochhaus, Ruediger Hehlmann, Philipp Erben, Thomas Ernst, Wolf-K. Hofmann, and Benjamin Hanfstein

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, Fusion Proteins, bcr-abl, Gene Expression, Gastroenterology, Piperazines, hemic and lymphatic diseases, Internal medicine, Humans, Medicine, ATP Binding Cassette Transporter, Subfamily B, Member 1, Treatment Failure, Protein Kinase Inhibitors, neoplasms, IC50, Aged, Neoplasm Staging, P-glycoprotein, Aged, 80 and over, biology, business.industry, Wild type, Myeloid leukemia, Imatinib, Hematology, Middle Aged, Prognosis, Pyrimidines, Treatment Outcome, Imatinib mesylate, Oncology, Nilotinib, Gene Knockdown Techniques, Benzamides, Leukemia, Myeloid, Chronic-Phase, Mutation, Immunology, Imatinib Mesylate, biology.protein, Female, RNA Interference, business, Tyrosine kinase, Follow-Up Studies, medicine.drug
Abstract

In the face of competing tyrosine kinase inhibitors (TKIs), identification of chronic myeloid leukemia (CML) patients expecting favorable response to second-line treatment is warranted. At the time of imatinib resistance, the investigation of multidrug-resistance protein 1 (MDR1) and BCR-ABL yielded the following results: (i) Patients with high MDR1 transcript levels showed superior response at 48 months as compared with low-level MDR1 patients: major molecular response (MMR) in 41% vs 16% (P=0.014), complete cytogenetic response (CCyR) in 58% vs 39% (P=0.044), and progression-free survival (PFS) in 67% vs 46% (P=0.032). (ii) Patients with BCR-ABL(IS)

Published
2014
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