The role of MDR‐related proteins in the prognosis of adult acute myeloid leukaemia (AML) with normal karyotype

Abstract

Cytogenetic abnormalities are among the most important factors affecting the outcome of patients with acute myeloid leukaemia (AML), but approximately 40-50% of AML cases display a normal karyotype at diagnosis. Multidrug resistance (MDR) proteins overexpression is associated with worse prognosis in acute leukaemias, but its role in normal karyotype AML is less defined. We analysed the expression of P-glycoprotein (PGP), MDR-related protein (MRP) and lung resistance protein (LRP) in 135 adult patients with normal karyotype AML and its correlation with other biological features of the disease, to evaluate the impact of MDR proteins on response to therapy and on survival. Increased PGP expression was associated with lower rate of complete remission (CR; p = 0.006), similarly to advanced age. Cases overexpressing PGP displayed also a shorter event-free survival (EFS; 4 vs. 10 months, p = 0.035) and the increased expression of at least one MDR protein was associated with a reduced overall survival (OS; p = 0.038). Also age was predictive of worse prognosis. Our data confirm the prognostic role of MDR proteins, in particular of PGP, also in AML patients with normal karyotype at diagnosis. This finding could be used to stratify patients with different prognosis and to design risk-adapted therapeutic strategies.

p53 flow cytometry evaluation in leukemias: Correlation to factors affecting clinical outcome

“…It was interesting to observe the strong association between p53 and Pgp expressions in AML samples. Pgp is a very well studied ABC transporter protein in AML being correlated with poor prognosis in a recent published work (30). Moreover, it has already been found a correlation between Pgp and p53 expressions (31).…”

Determination of P‐glycoprotein, MDR‐related protein 1, breast cancer resistance protein, and lung‐resistance protein expression in leukemic stem cells of acute myeloid leukemia

“…Kolgomorov-Smirnov (D) and Mean Fluorescence Index (MFI) values are represented as mean 6 Standard Deviation factor associated with reduced remission rates with anthracycline containing regimens, and in some reports, inferior leukemia-free and overall survival (23)(24)(25)(26). In contrast, functional MDR assays have failed to show greater prognostic value in larger studies (12).…”

Advances in investigations on the mechanism of cancer multidrug resistance and the liposomes-based treatment strategy

“…Among these transporters, P-glycoprotein (P-gp) is the first discovered and has attracted the most attention of scientists (Juliano and Ling 1976). Actually, nearly 40-50 % of the patients diagnosed with cancer have overexpression of P-gp in the tumor tissues, and cases overexpressing P-gp also displayed a shorter event-free survival (Damiani et al 2007). P-gp protein has been isolated from the plasma membrane of highly drug resistant CH R B30 cell line (Chinese hamster ovary cell), and reconstituted into the proteoliposomes as a model for studying the translocation of phospholipids (or drugs) from the outer to the inner leaflet of the bilayer (Romsicki and Sharom 2001).…”