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

Abstract

BACKGROUND AND OBJECTIVES: We studied the function of both Pgp and MRP1 to identify subgroups of patients who could benefit from Pgp reversion, and to clarify in different FAB subtypes and in cytogenetic risk groups their expression and function. DESIGN AND METHODS: We examined 132 adults with de novo acute myeloid leukemia (AML) for Pgp and MRP1 expression and function. We correlated our finding with the FAB subtypes and the cytogenetics, and clinical data of our patients. RESULTS: Among FAB subtypes and cytogenetic subgroups, patients with good risk cytogenetics have a low expression and activity of Pgp and MRP1 except patients with inv(16) who have a higher activity of MRP1 than t(8;21) and t(15;17) (p=0.05). All other AML patients, except M5, have a high expression and activity of Pgp. In contrast, M5 have a high expression, but a low activity of Pgp. In this subgroup, M5 with MLL gene rearrangement did not express an active Pgp. Others patients with M5 AML did not have a functional Pgp. Monosomy 7, 11q2.3 gene rearrangement and complex cytogenetic have a higher activity of MRP1 than other cytogenetic (p=0.03). INTERPRETATION AND CONCLUSIONS: 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(16). Thus trials that modulate Pgp are likely to achieve limited success in AML with low activity of Pgp, i.e., M5 and, AML with good risk cytogenetics.