Function of the ABC transporters, P-glycoprotein, multidrug resistance protein and breast cancer resistance protein, in minimal residual disease in acute myeloid leukemia
| Autor: | Marjolein A, van der Pol, Henk J, Broxterman, Jennie M, Pater, Nicole, Feller, Martin, van der Maas, Geert W D, Weijers, George L, Scheffer, John D, Allen, Rik J, Scheper, Arnold, van Loevezijn, Gert J, Ossenkoppele, Gerrit J, Schuurhuis |
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| Rok vydání: | 2003 |
| Předmět: |
Adult
ATP Binding Cassette Transporter Subfamily B Neoplasm Residual Middle Aged Prognosis Neoplasm Proteins Drug Resistance Neoplasm Leukemia Myeloid Acute Disease ATP Binding Cassette Transporter Subfamily G Member 2 Humans ATP-Binding Cassette Transporters ATP Binding Cassette Transporter Subfamily B Member 1 Longitudinal Studies Aged |
| Zdroj: | Haematologica. 88(2) |
| ISSN: | 0390-6078 |
| Popis: | Relapse is common in acute myeloid leukemia (AML) because of persistence of minimal residual disease (MRD). ABC-transporters P-glycoprotein (Pgp) and multidrug resistance protein (MRP), are thought to contribute to treatment failure, while it is unknown whether breast cancer resistance protein (BCRP) does so. However, whether up-regulation of pump activity or selection of subpopulations with higher pump activity occurs during chemotherapy is unclear. The aim of this study was to elucidate whether ABC-transporter function changes during the course of disease.MRD cells were identified using leukemia-associated phenotypes combined with a fluorescent probe assay with substrate/modulator: Syto16/ PSC833 (Pgp), calcein-AM/probenecid (MRP) and BODIPY-prazosin/Ko143 (BCRP); efflux profiles were directly compared with blasts at diagnosis and relapse from the same patient.At diagnosis BCRP activity was undetectable in AML blasts from 23/26 cases, while Pgp activity was present in 36/45 and MRP activity in 26/44 of the cases. Furthermore, no subpopulations of blasts with considerably higher drug efflux capacities were found. Overall, no consistent changes were observed at follow-up [during chemotherapy (n=20), MRD (n=37), relapse (n=26))] in forty-five patients, the mean activities (as percentages of values at diagnosis) were 97% (Pgp), 103% (MRP) and 102% (BCRP).Emergence of MRD is thus not accompanied by either upregulation of ABC-transporter function during or after chemotherapy or by selection of pre-existing highly resistant subpopulations. The prognostic value of Pgp and MRP is, therefore, likely related to drug efflux capacity homogeneously distributed in the whole blast population, while BCRP probably has a limited function in drug efflux-related resistance in AML. |
| Databáze: | OpenAIRE |
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