Deletion of the multidrug resistance gene
MRP1 has been demonstrated in
acute myeloid leukemia (AML) patients with inversion of chromosome 16 (inv[16]). These AML patients are known to have a relatively favorable prognosis, which suggests that
MRP1 might play an important role in determining clinical outcome. This study analyzed
MRP1 deletion by fluorescent in situ hybridization (FISH), with a focus on inv(16) AML patients. Functional activity of multidrug resistance
protein (MRP) was studied in a flow cytometric assay with the use of the MRP substrate
carboxyfluorescein (CF) and the inhibitor
MK-571.
MRP1, MRP2, and MRP6
messenger RNA (
mRNA) expression was determined with
reverse transcriptase-polymerase chain reaction (RT-PCR). The results were compared with normal bone marrow cells.
MRP1 deletion was detected in 7 AML patients; 2 cases showed no
MRP1 FISH signals, and 5 cases had 1
MRP1 signal, whereas in 4 AML patients with inv(16) no
MRP1 deletions were observed. A variability in MRP activity, expressed as CF efflux-blocking by
MK-571, was observed (efflux-blocking factors varied between 1.2 and 3.6); this correlated with the number of
MRP1 genes (r = 0.91, P <. 01). MRP activity in the AML cases was not different from normal hematopoietic cells.
MRP1 mRNA was detected in patients with 1 or 2
MRP1 FISH signals, but not in patients with no
MRP1 signals. MRP2 and MRP6
mRNA were expressed predominantly in AML samples with 1
MRP1 signal, whereas in normal bone marrow cells no MRP2 and MRP6
mRNA was observed. In conclusion, this study shows that MRP activity varies among inv(16) AML cases and does not differ from that in normal hematopoietic cells; this might be in part due to the up-regulation of other MRP genes.