P-glycoprotein and multidrug resistance associated protein-1 activity in 132 acute myeloid leukemias according to FAB subtypes and cytogenetic risk groups

Background and Objectives. We studied the function of both P-glycoprotein (Pgp) and multidrug resistance associated protein-1 (MRP1) to identify subgroups of patients who could benefit from Pgp reversion, and to clarify the expression and function of these proteins in different FAB subtypes and cytogenetic risk groups. Design and Methods. We examined Pgp and MRP1 expression and function in 132 adults with de novo acute myeloid leukemia (AML). We correlated our findings with the FAB subtypes and cytogenetic risk groups, and clinical data of our patients. Results. Patients with good risk cytogenetics have low expression and activity of Pgp and MRP1 except patients with inv(16) who have a higher activity of MRP1 than do patients with t(8;21) and t(15;17) (p=0.05). All other AML patients, except those with M5, have high expression and activity of Pgp. In contrast, patients with M5 AML have a high expression, but low activity of Pgp. In this subgroup, patients with M5 AML and MLL gene rearrangement did not express active Pgp. Others patients with M5 AML did not have functional Pgp. Patients with monosomy 7, 11q2.3 gene rearrangement and complex cytogenetics have higher activity of MRP1 than those with other cytogenetic findings (p=0.03). Interpretation and Conclusions. The resistance mechanism in M5 was not mediated by Pgp. In contrast, MRP1 may play a role in patients who have a 11q2.3 gene rearrangement, or in M4E with inv(1 6). Thus trials that modulate Pgp are likely to achieve limited success in cases of AML with low activity of Pgp, i.e., M5, and AML with good risk cytogenetics.