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Showing 4 results for Drug Resistance
Multiple drug resistance in acute myelocytic leukemia/acute lymphocyte leukemia patients and MDR evaluation
Dr. K. Ali Moghadam, Dr. M. Alami Samimi, A. Ashori, Dr. M. Toutounchi, Dr. M. Farhadi Langroudi, Dr. F. Nadali, Dr. M. Iravani, S.a. Mousavi, Dr. A. Khodabandeh, Dr. M. Jahani, Dr. A. Ghavamzadeh,
Volume 5, Issue 1 (3-2008)
Abstract

  Abstract

 Background and Objectives

 Drug resistance is a common cause of treatment failure in malignant disorders especially hematological malignancies. Overexpression of P-glycoprotein (pgp) is the most common cause of drug resistance. Studies on the importance of pgp are controversial that is attributed to the lack of a standard method for pgp assay and the lack of consistency with clinical data. The aim of this study is Multiple drug resistance (MDR) evaluation according to pgp expression in leukemic cells at the beginning of treatment, and prediction of responses to treatment, relapse or death.

 

 Materials and Methods

 Between June 2001 and May 2006, we studied 185 leukemic patients. Diagnosis was performed on each case via morphology, based on immunotypes, and by cytogenetic method pgp expression was also evaluated by flowcytometry. For pgp evaluation, we collected peripheral blood or bone marrow samples in EDTA. Then, patients went under treatment by standard protocols and their responses to treatment were observed. Patient follow ups for response to treatment, complete remission, resistance to induction, relapse or death were conducted. Finally, clinical data were compared with laboratory results. Mann-Whitney, kruscal-valis, kaplan-meier, and chi-square tests were used for data analysis.

 

 Results

 From 185 patients with the median age of 28.5 years (within the age range of 11-76), 128 patients showed AML and 57 ALL. 62% were male and 38% female. Pgp expression showed no significant correlation with age, sex, type of leukemia, and white blood cells count. There was no significant association between pgp expression and AML subtype. Two-year Overall Survival (OS) and Disease Free Survival (DFS) were 63% and 42% respectively. DFS showed significant correlation with pgp in ALL and non-M3 subtype of AML (P=0.024).

 

 Conclusions

 Expression of pgp would be a prognostic factor for relapse prediction and might be important in treatment planning.

 �

 Key words : Multiple drug resistance, P-Glycoprotein, Acute myelocytic leukemia, Acute lymphocytic leukemia

 


Evaluation of the expression profile of MDR1 geneand assessment of its prognostic value in childhood ALL
M. Anedi, Dr. S. Rahgozar, Dr, A.r. Moafi, Dr. K. Ghaedi, Dr. S.j. Moshtaghian, M.s. Entezar-E-Ghaem, F. Montazeri,
Volume 10, Issue 4 (1-2014)
Abstract
Abstract Background and Objectives Acute lymphoblastic leukemia (ALL) is the most common cancer among children. Multi drug resistance (MDR) is the major cause of treatment failure and relapse in ALL. ABC transporters mainly contribute to this disorder and MDR1 gene is the most popular member of this family. The aim of this study is to evaluate the gene expression profile of MDR1 at mRNA level and its prognostic value in ALL. Materials and Methods Bone marrow and peripheral blood samples were obtained from 28 newly diagnosed ALL patients and 15 controls. MDR1 gene expression profile was evaluated by using real time PCR. The minimal residual disease (1-year MRD) was considered as the factor of response to therapy. Data were analyzed by using SPSS 20 and Graph Pad Prism 5 softwares. Results MDR1 gene expression level in patients with MRD+ was significantly higher than MRD- patients (2.29 ± 1.22 vs 0.79 ± 0.21)(mean ± SEM, p= 0.049). Most of the patients with over expression of MDR1 gene were MRD+ (66.6% vs 33.3)(mean ± SEM, p= 0.048). Conclusions MDR1 gene expression profile is suggested to be an unfavorable prognostic factor in ALL. The evaluation of the mRNA expression profile of MDR1 in new case patients facilitates identification of the high risk patients and helps modifying the protocols applied for ALL treatment in order to improve the therapeutic outcome.
Investigation of G2677T/A polymorphism in MDR1 gene of childhood acute lymphoblastic leukemia
N. Mokhberian, F. Mahjoubi, R. Pourahmad,
Volume 11, Issue 2 (6-2014)
Abstract

  Abstract

 Background and Objectives

 The important reason of drug resistance is ATP dependent pumps such as MDR1 that extrudes drugs from the cell. MDR1 is highly polymorphic. It seems that polymorphisms influence the gene expression and response to treatment. The aim of this study was to investigate G2677T/A polymorphism of the MDR1 gene and its association with the response of treatment in childhood acute lymphoblastic leukemia. 

 

 Materials and Methods

 In this descriptive study, G2677T/A polymorphism of MDR1 was investigated in 44 children with acute lymphoblastic leukemia and 40 healthy individuals by the ARMS-PCR technique. The association of this polymorphism with response to treatment was also investigated .

 

 Results

 In the patient group, the frequencies of genotypes were 36.4% for TT, 41% for GT, 13.6% for GG,4.5% for AG, 2.25% for AT and 2.25 % for AA whereas in the control group the frequencies were 35%, 37.5% , 10%, 7.5%, 5% , and 5% for TT, GT, GG, AG, AT, and AA, respectively . There was no significant difference in the frequencies of G2677T/A polymorphism between patients and the healthy group. Neither was there any significant difference between the frequency rates of G2677T/A polymorphism of MDR1 in the responder and the non responder .

 

 Conclusions

 It seems that there is no correlation between G2677T/A polymorphism of MDR1 gene and response to treatment. So the role of G2677T/A polymorphism in the gene expression of MDR1 in childhood acute lymphoblastic leukemia and response to treatment is still controversial.

 

 


The Significance of Ubiquitin-Proteasome Pathway in Glucocorticoid Resistance Development in Acute Lymphoblastic Leukemia
Dr. N. Dehghan Nayeri, Dr. P. Eshghi, Dr. K. Goudarzi Pour, M. Darvishi, Dr. َ. Gharehbaghian,
Volume 15, Issue 2 (6-2018)
Abstract
Abstract
Background and Objectives
ALL is the most common malignancy in childhood. Presently, approximately 20% of patients do not respond to treatment due to the resistance of leukemia blasts. Response to GCs is considered as the strongest independent factor in predicting ALL patients outcome. Therefore, identification of GCs resistance markers are the beneficial tools for improvement of prognostic strategies in ALL.
 
Materials and Methods
In this experimental study,  the protein-protein interaction network of fourteen significant down or up-regulated proteins in the proteome of human lymphoblastic cell treated with prednisolone and dexamethasone were analyzed by using the STRING online database.
 
Results
By using proteomics methods, fourteen down or up-regulated proteins, SRSF3, CNBP, VDAC1, SNX3, PFDN6, PSMB2, STMN1, PPP4R4, DUT, CAPZA1, CAPZB, PNP, CLIC1 and PSME1 were recognized in both the sensitive and resistant GC cell lines. Correlation between these proteins were analyzed by using the STRING database.
 
Conclusions 
Overall, the findings showed that the Ubiquitin-Proteasome pathway plays a pivotal role in inducing resistance to GC in ALL. Therefore, the study of key controlling proteins in this pathway can play an important role in clarifying the mechanisms of induction of resistance to GC and consequently the prognosis of the disease.
 
 

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