[Show abstract][Hide abstract] ABSTRACT: Overexpression of the multidrug resistance-associated protein 1 (MRP1) gene has been linked with resistance to chemotherapy in vitro, but little is known about its clinical impact on acute leukemia patients. Our aim was to investigate the possible association between MRP1 gene expression level and clinical outcomes among Iranian leukemia patients.
This was an analytical cross-sectional study on patients referred to the Hematology, Oncology and Stem Cell Research Center, Sharyatee Public Hospital, whose diagnosis was acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL). All molecular work was performed at NIGEB (public institution).
To correlate with prognostic markers and the clinical outcome of acute leukemia, MRP1 gene expression was assessed in 35 AML cases and 17 ALL cases, using the quantitative real-time polymerase chain reaction and comparing this to the chemotherapy response type.
Mean expression in AML patients in complete remission (0.032 +/- 0.031) was significantly lower than in relapsed cases (0.422 +/- 0.297). In contrast, no significant difference in MRP1 mRNA level was observed between complete remission and relapsed ALL patients. There was a difference in MRP1 expression between patients with unfavorable and favorable cytogenetic prognosis (0.670 +/- 0.074 and 0.028 +/- 0.013, respectively). MRP1 expression in M5 was significantly higher (p-value = 0.001) than in other subtypes.
The findings suggest that high MRP1 expression was associated with poor clinical outcome and was correlated with the M5 subtype and poor cytogenetic subgroups among AML patients but not among ALL patients.
Preview · Article · Jun 2008 · Sao Paulo Medical Journal
[Show abstract][Hide abstract] ABSTRACT: The 40-bp VNTR polymorphism in the 3' untranslated region of the human DAT1 (dopamine transporter 1) was analyzed in the Iranian ethnic groups in order to examine the influence of geographical and linguistic affiliation on the genetic affinities among the Iranian population. A total of 449 subjects belonging to nine ethnic groups from the Iranian population were included in the study. The screening of 898 chromosomes showed five alleles (6, 7, 8, 9, 10, and 11), of which allele 10 revealed the highest frequency in most regions. Allele 8 was predominant in one ethnicity and occurred more frequently in the center of Iran. This study shows that the DAT1 distribution in Iran has a different pattern from those in other studies, which can contribute to an understanding of differentiation and diversity of Iranian ethnic groups. This polymorphism could represent the genetic diversity among the various ethnic groups of Iran.
No preview · Article · Nov 2007 · American Journal of Human Biology
[Show abstract][Hide abstract] ABSTRACT: Upregulation of multidrug resistance-associated protein (MRP1) gene has been detected in many in vitro systems and could be the basis of the drug resistance phenotype in vivo. Increase in gene dosage and overexpression are two major mechanisms for increasing MRP1 expression level. In many drug resistant cell lines, MRP1 gene amplification has been detected. However, it is not yet known whether gene amplification plays a role in inducing the multidrug resistance phenotype clinically.
To establish whether MRP1 gene copy number is a common feature of the upregulation of MRP1 expression in cancer patients, we studied the MRP1 gene copy number in leukemia patients by fluorescent in situ hybridization (FISH) and real-time PCR. This involved determination of the MRP1 gene copy number and mRNA level in the peripheral blood of 52 adult leukemic patients and ten healthy volunteers. The leukemic CCRF-CEM cell line (drug sensitive) and its drug-resistant subline CCRF-E1000, which has MRP1 overexpression, were used as controls.
The MRP1 gene copy number in CCRF-CEM was normal but increased significantly in CCRF-E1000 cell line. However, in the presence or absence of MRP1 overexpression, increase in gene dosage was not detected in patients.
Our data suggest that the increase in MRP1 gene dosage observed in resistant cell lines is not responsible for the upregulation of MRP1 expression in leukemic patients.
No preview · Article · May 2007 · Archives of Medical Research