Quantitative molecular monitoring of BCR-ABL and MDR1 transcripts in patients with chronic myeloid leukemia during Imatinib treatment

Different mechanisms could sustain Imatinib resistance, including overexpression of MDR1, a gene already known to be responsible for multidrug resistance in other hematologic malignancies. In search for a possible correlation, BCR-ABL and MDR1 expression were measured in 115 serial bone marrow sampl...

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Published in:Cancer genetics and cytogenetics 2005-10, Vol.162 (1), p.57-62
Main Authors: Galimberti, Sara, Cervetti, Giulia, Guerrini, Francesca, Testi, Rossana, Pacini, Simone, Fazzi, Rita, Simi, Paolo, Petrini, Mario
Format: Article
Language:English
Subjects:
Adult
Aged
Benzamides
Drug Resistance, Neoplasm
Female
Fusion Proteins, bcr-abl - metabolism
Genes, MDR
Humans
Imatinib Mesylate
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy
Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics
Male
Middle Aged
Piperazines - therapeutic use
Pyrimidines - therapeutic use
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
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Summary:Different mechanisms could sustain Imatinib resistance, including overexpression of MDR1, a gene already known to be responsible for multidrug resistance in other hematologic malignancies. In search for a possible correlation, BCR-ABL and MDR1 expression were measured in 115 serial bone marrow samples from 33 CML patients during Imatinib treatment. All patients achieved complete hematologic responses, and 22 patients also achieved complete cytogenetic responses, with median BCR-ABL mRNA values significantly lower than those observed in the group of cases that were persistently Philadelphia positive. All three cases treated during the accelerated phase showed disease progression after an initial period of remission; all presented either increased levels of BCR-ABL or MDR1 3 months before clinical progression. In the subgroup of cases treated during the chronic phase, BCR-ABL and MDR1 levels were significantly correlated after 3 and 6 months (88 and 80%, respectively) but not after 12 months of treatment (32%). Reported data maintain that MDR1 expression would play an important role in Imatinib resistance when the disease is not fully controlled (e.g., progressive disease or during the first months of treatment).
ISSN:0165-4608
1873-4456
DOI:10.1016/j.cancergencyto.2005.01.015