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International Journal of Hematology-Oncology and Stem Cell Research، جلد ۱۲، شماره ۱، صفحات ۱۴-۲۲

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عنوان انگلیسی Association between Altered Expression and Genetic Variations of Transforming Growth Factor β-Smad Pathway with Chronic Myeloid Leukemia
چکیده انگلیسی مقاله Background: Chronic myeloid leukemia (CML) is a hematological disorder caused by fusion of BCR and ABL genes. BCR-ABL dependent and independent pathways play equally important role in CML. TGFβ-Smad pathway, an important BCR -ABL independent pathway, has scarce data in CML. Present study investigate the association between TGFβ-Smad pathway and CML. Materials and Methods: Sixty-four CML patients and age matched healthy controls (n=63) were enrolled in this study. Patients were segregated into responder and resistant groups depending on their response to Imatinib mesylate (IM). TGFβ1 serum levels were evaluated by ELISA and transcript levels of TGFβ1 receptors, SMAD4 and SMAD7 were evaluated by Real-Time PCR. Sequencing of exons and exon-intron boundaries of study genes was performed using Next Generation Sequencing (NGS) in 20 CML patients. Statistical analysis was performed using SPSS version 16.0. Results: TGFβ1 serum levels were significantly elevated ( p = 0.02) and TGFβR2 and SMAD4 were significantly down-regulated ( p = 0.012 and p = 0.043 respectively) in the patients. c.69A>G in TGFβ1 , c.1024+24G>A in TGFβR1 and g.46474746C>T in SMAD7 were the most important genetic variants observed with their presence in 10/20, 8/20 and 7/20 patients respectively. In addition, TGFβR1 transcript levels were reduced in CML patients with c.69A>G mutation. None of the genes differed significantly in terms of expression or genetic variants between responder and resistant patient groups. Conclusion: Our findings demonstrate the role of differential expression and genetic variants of TGFβ-Smad pathway in CML. Decreased TGFβR2 and SMAD4 levels observed in the present study may be responsible for reduced tumor suppressive effects of this pathway in CML.
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نویسندگان مقاله yogender shokeen | yogender shokeen
school of biotechnology and biosciences, lovely professional university, jalandhar, punjab, india


neeta راژ شارما | neeta raj sharma
department of research, sir ganga ram hospital, rajinder nagar, delhi, india


abhishek vats | abhishek vats
department of research, sir ganga ram hospital, rajinder nagar, delhi, india


veronique dinand | veronique dinand
department of research, sir ganga ram hospital, rajinder nagar, delhi, india


میرزا عادل beg | mirza adil beg
strand center for genomics and personalized medicine, uas alumni building, veterinary college campus, bellary road, hebbal, bangalore, india


satish sanskaran | satish sanskaran
department of medical oncology, sir ganga ram hospital, delhi, india


sachin minhas | sachin minhas
department of medical oncology, sir ganga ram hospital, delhi, india


mayank jauhri | mayank jauhri
strand center for genomics and personalized medicine, uas alumni building, veterinary college campus, bellary road, hebbal, bangalore, india


arun k hariharan | arun k hariharan
department of research, sir ganga ram hospital, rajinder nagar, delhi, india


vibha taneja | vibha taneja
department of medical oncology, sir ganga ram hospital, delhi, india


شیام aggarwal | shyam aggarwal



نشانی اینترنتی http://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/758
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