Expression of Multidrug Resistance 1, Lung Resistance Protein and Breast Cancer Resistance Protein Genes in Chronic Leukemias

Abstract

One of the major problems in treatment of leukemias is multidrug resistance, which is already present at diagnosis or develops after chemotherapy. The gene expression levels of multidrug resistance resistance 1 (MDR1), breast cancer resistance protein (BCRP) and lung resistance-resistance protein (LRP) were evaluated in blood samples of 20 CLL and 24 CML patients using RT-PCR. MDR1, BCRP and LRP expression levels were detected in 65%, 20% and 45% of CLL patients, and in 54%, 37% and 25% of CML patients, respectively. 20% of CLL patients and 33% of CML patients expressed none of the genes. The other 20% of CLL patients expressed all the genes. 17% of CML patients expressed all of these genes, and two of them rapidly progressed to acute leukemia. MDR and LRP expressions seem to be frequent events in CLL and CML patients; however no conclusion can be drawn on their prognostic role and response to the treatment. Lösemi tedavisinde en önemli problemlerden birisi hastada zaten var olan veya kemoterapi s›ras›nda geliflen, kemoterapötik ilaçlara karfl› ilaç direncinin geliflmesidir. Çoklu ilaç dirençlili¤i genleri olan MDR1, BCRP, LRP gen ifadeleri 20 KLL ve 24 KML hastas›nda GT-PZR metoduyla belirlenmifltir. Çoklu ilaç dirençlili¤i genleri olan MDR1, BCRP, LRP gen ifadeleri 20 KLL ve 24 KML hastas›nda GT-PZR metoduyla belirlenmifltir. MDR1, BCRP ve LRP gen ifade düzeyleri KLL vakalar›n›n s›ras›yla %65, %20 ve %45'inde; KML vakalar›n›n ise %54, %37 ve %25'inde bulunmufltur. KLL vakalar›n›n %20'sinde ve KML vakalar›n›n %33'ünde ise genlerin ifadeleri gözlenmemifltir. KLL hastalar›n›n di¤er %20'si ise incelenen genleri ifade etmifllerdir. KML hastalar›n›n %17'si her üç geni ifade etmifller ve hastalardan ikisi akut lösemiye h›zl› bir flekilde geçifl göstermifllerdir. MDR1 ve LRP gen ifadelerinin KLL ve KML için anlaml› oldu¤u anlafl›lmaktad›r. Ancak, gen ifadelerinin prognostik önemlerinin belirlenebilmesi aç›s›ndan anlaml› bir sonuç ç›kar›lamam›flt›r. ficant association was found between the treatment and the expression of the other resistance related genes (BCRP, LRP). According to Mann-Whitney test for continuous variables, the median of disease age for patients with observed MDR1 expression was significantly lower than the median of disease age for patients with no MDR1 expression (p= 0.014). However the distribution of age was not significantly different in patients with or without MDR1 expression. The distribution of neither age nor disease age was significantly different for patients with or without BCRP and LRP gene expressions. According to Fisher's exact test for gene expression associations, there was no significant association among three genes analyzed. Resistance related gene expression of CML patientsThe ages of the patients were between 24 and 71 with a median of 41 years, and the time from diagnosis up to RNA isolation varied between less than 1 to 12 years with a median of 2 years (Table 1). Eighteen of 24 patients had chemotherapy at the time of blood sampling. Details of chemotherapy given to p...

Expression of LRP Gene in Breast Cancer Patients Correlated with MRP1 as Two Independent Predictive Biomarkers in Breast Cancer

“…Overexpression of MRP1 has been observed in several human cancers, including breast cancer, gastric hepatoid adenocarcinoma, and several types of leukemia (Faneyte et al, 2004;Mahjoubi et al, 2008;Iseri et al, 2011). We previously found and reported a significant positive correlation between MRP1 expression and response to treatment and the importance of MRP1 rather than MDR1 in breast cancer patients (Taheri and Mahjoubi, 2013).…”

Exploring a natural MDR reversal agent: potential of medicinal food supplement Nerium oleander leaf distillate

“…However acquired drug resistance during chemotherapy limits the success of chemotherapy. This situation is known as multiple drug resistance (MDR) [2,3] .…”

“…Nerium oleander L. (N. oleander) is an important plant used in medicine. N. oleander is a tree, middle in length [2][3][4][5] m, evergreen and with flower. This plant is actually a Mediterranean and tropical Asian tree [5] .…”

“…Resistance developed against chemotherapy causes an ineffective therapy period and progress of the disease [3] . There are various natural compounds being used in cancer therapy [4] .…”