P‐glycoprotein and multidrug resistance‐associated protein‐1 expression in acute myeloid leukemia: Biological and prognosis implications

Abstract

Background Despite the advances in the cure rate for acute myeloid leukemia (AML), a considerable number of patients die from the disease due to the occurrence of multidrug resistance (MDR). Overexpression of the transporter proteins, such as P‐glycoprotein (Pgp) and multidrug resistance‐associated protein (MRP), confers resistance to the treatment of these leukemias. Methods To analyze the expression of the Pgp and MRP1 in patients with AML and determine their correlation between expression and demographic, clinical, and laboratorial variables, bone marrow and peripheral blood samples from 346 patients with a diagnosis of AML were assessed for the expression of Pgp and MRP1 by flow cytometry. Results The expression of Pgp and MRP1 was found in 111 (32.1%) and 133 (38.4%) patients, respectively, with greater prevalence in older patients and lower in children, while also observing a high incidence in patients with refractory, recurrence, and secondary disease in comparison with the cases of de novo AML. Regarding the laboratory findings, we observed an association between the expression of Pgp and MRP1 and CD34, CD7, and also M7, M5a, and M2‐AML of French‐American‐British classification. Conclusions The results showed that the detection of MDR phenotype by flow cytometry can be a molecular marker for prognosis of patients with AML.

Long noncoding RNA HULC contributes to paclitaxel resistance in ovarian cancer via miR-137/ITGB8 axis

“…As shown in Figure 2c and d , the expression level of HULC declined more than 70% in PTX-resistant OC cells transfected with si-HULC. Several drug transporter proteins in tumor cells, including P-gp and GST-π, are involved in the chemotherapy resistance [ 26 , 27 ]. We further investigated the protein levels of P-gp and GST-π in PTX-resistant OC cells with HULC knockdown.…”

Inhibitors of Chemoresistance Pathways in Combination with Ara-C to Overcome Multidrug Resistance in AML. A Mini Review

“…These MOCs can reduce drug entry into the cytoplasm of leukemic cells by hindering either the expression, function or both, of the solute carriers responsible for drug absorption, or they can increase the ability of tumor cells to export pharmacologically active agents, which are exported by pumps or efflux transporters belonging to the ATP-binding cassette superfamily (ABCC4, ABCC10 and ABCC11). Another group of MOCs can lead to a decreased ratio of active versus inactive agents within tumor cells due to changes in either the expression, function or both, of enzymes responsible for prodrug activation or drug inactivation [ 29 , 31 , 32 ]. Other mechanisms that affect the response to chemotherapy include changes in the expression or function of the molecular targets of anticancer drugs; an increase in the ability of cancer cells to repair the DNA damage induced by anticancer drugs; either decreased expression, function or both of proapoptotic factors; upregulation of antiapoptotic genes; and increased responses to stress and changes in the leukemic cellular microenvironment [ 29 ].…”

“…Likewise, the efflux pumps ABCC4 (MRP4), ABCC10 (MRP7) and ABCC11 (MRP8) have been linked to Ara-C resistance because they are transporters of this drug and can decrease its concentration in AML cells ( Figure 3 a). One strategy to limit the ability of cells to exclude Ara-C and its monophosphorylated form (Ara-CMP) is to inhibit the functioning of ABCC4, a transmembrane protein belonging to the ATP-binding cassette transporter superfamily (ABC) and highly expressed in AML [ 31 , 37 , 51 , 67 , 78 ]. ABCC4 inhibition can be accomplished with the use of inhibitors such as sorafenib or MK571 or by silencing it with siRNA ( Figure 3 b).…”

Piceatannol, a Structural Analog of Resveratrol, Is an Apoptosis Inducer and a Multidrug Resistance Modulator in HL-60 Human Acute Myeloid Leukemia Cells

“…Another important therapeutic strategy recently introduced for AML treatment is based on the use of hypomethylating agents (HMA) such as decitabine [8]. The major problems of chemotherapy of AML are treatment-related toxicity and mortality, cellular heterogeneity, as well as the occurrence of multidrug resistance (MDR) [5][6][7][8][9][10]. MDR results from the overexpression of transport proteins belonging to the ATP-binding cassette (ABC) superfamily [11][12][13][14].…”

“…There are many well-characterized ABC efflux pumps including P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein (BCRP) [12,[20][21][22][23][24][25][26][27]. Accumulating evidence suggests that P-gp, MRP1 and BCRP expression may be involved in multidrug resistance in AML [9,10,[28][29][30][31][32][33].…”