Expression of the multiple drug resistance associated genes : MRP1, LRP and BCRP among leukemia patients in Gaza Strip

Other Title(s)

التعبير الجيني للجينات المقاومة للعقاقير (MRP1, LRP and BCRP)‎ عند مرضى اللوكيميا في قطاع غزة

Dissertant

al-Sadoni, Hani

Thesis advisor

Abid, Abd Allah A.
Ayish, Basim Muhammad

University

Islamic University

Faculty

Faculty of Science

Department

Department of Biological Science

University Country

Palestine (Gaza Strip)

Degree

Master

Degree Date

2010

English Abstract

Hematological neoplasms are usually sensitive to chemotherapy, but with relatively high rate of relapse.

Cell resistance to drugs is a major determinant of response to chemotherapy and its detection may be of clinical relevance.

The role of expression of trans membrane carriers such as multidrug resistance related Protein 1 (MRP1), breast cancer resistance protein (BCRP) and lung resistance protein (LRP) genes in neoplastic cell survival and risk of relapse for leukemia patients was previously documented.

Therefore, the aim of this study was to estimate the level of expression of MRP1, BCRP, and LRP genes in blood cells of leukemia patients in Gaza strip by quantitative real-time RT-PCR technique, and to investigate any correlation between the expression of these genes and other previous and current clinical findings of the patient. Blood samples were collected from 70 leukemia patients (40 males and 30 females) admitted in the Hematology Departments of Al-Shefa hospital, the European Gaza Hospital and AL-Nasser pediatric hospital in Gaza strip.

The specimens were collected during the period between May to November, 2009 Patients medical data were obtained from their records in the relevant hospitals, and included personal, medical, management and family information (e.g.

age, type of disease, severity of case, date of disease, types, protocols of treatments prognosis, previous tests results and others).

A control group of 35 normal healthy individuals was included mainly to correct for any inter-individual expression difference as a result of gender and age variation.

This group was also used to compare the levels of gene expression in normal and leukemia patients.

The level of expression of MRP1, LRP, and BCRP genes in cells of leukemia patients were quantitated by quantitative Real Time-PCR technique and normalized by the expression level of an endogenous control gene porphobilinogen deaminase (PBGD).

The SPSS version 15 was used for statistical analysis. Five types of leukemia, from different areas of Gaza strip, were included in this study.

Thirty cases (42.9 %) were acute lymphoblastic leukemia, 5 cases (7.1 %) acute meroblastic leukemia, 12 cases (17.1 %) chronic lymphoblastic leukemia, 22 cases (31.4 %) chronic meroblastic leukemia and 1 case (1.4 %) small lymphoblastic leukemia.

The mean age of cases was 32.9 ± 28.2 years and the mean age of controls was 27.2 ±18.8 years. MRP1 and LRP but not BCRP mean level of gene expression was significantly higher in leukemia group than normal control group.

MRP1 gene expression in ALL patients was lower than all types of leukemia and significantly lower than in AML (P = 0.00).

LRP gene expression was significantly higher in AML and CML patients than in control group (AML : P = 0.021 and CML : P = 0.001).

LRP gene expression in ALL patients were significantly lower than CML patients (P = 0.024) ; and in CML patients higher than CLL patients (P = 0.046).

There was no statistically significant difference between leukemia types in BCRP gene expression levels.

MRP1 and LRP mean levels of expression in remission was less than with no remission patients and this decrease of expression was statistically significant (MRP1 : P = 0.003 and LRP : P = 0.050).

The mean level of BCRP gene expression in remission patients was also less but with no statistical significance.

When comparing the level of MRP1, LRP and BCRP according to management protocols and gender of patient no significant relationship was established.

The outcome of the current study indicates that higher levels of MRP1, LRP and BCRP expression are correlated with chemotherapeutic treatment failure of leukemia patients.

Therefore we suggest these factors to be included in the design and application of chemotherapy protocols in Gaza Strip.

Main Subjects

Medicine

Topics

• Leukemia
• Palestine
• Gaza Strip

No. of Pages

98

Table of Contents

• APA
• MLA
• AMA

Language

English

Data Type

Arab Theses

Record ID

BIM-303486