مجله علوم پزشکی پارس

تغییر بیان ژن DNMT3A در لوسمی لنفوبلاستیک حاد نوع B در اثر داروی مرکاپتوپورین

نویسندگان

دانشگاه علوم پزشکی شهید صدوقی یزد

چکیده

مقدمه: داروهای امروزی درمان لوسمی لنفوبلاستیک حاد (acute lymphoblastic leukemia, ALL) از جمله مرکاپتوپورین، عوامل مولکولی دخیل در فرآیند ایجاد و پیشرفت این بیماری مثل DNA متیل ترانسفرازها (DNMT) را هدف قرار داده اند زیرا این آنزیم ها در متیلاسیون و در نتیجه تنظیم بیان ژن های مرتبط با تکثیر سلولی دخیلند. در این مطالعه اثر مرکاپتوپورین بر بیان ژن DNMT3A بررسی شد.
روش کار: مطالعه به صورت تحلیلی قبل و بعد روی هشت کودک مبتلا به ALL نوع B مراجعه کننده به بیمارستان مرکز طبی کودکان تهران بصورت نمونه گیری در دسترس (convenience) در مرحله قبل از دریافت داروی مرکاپتوپورین و دو ماه پس از دریافت دارو، و ۱۰ کودک سالم مراجعه کرده به آزمایشگاه مرکزی یزد انجام شد. از نمونه خون ها RNA استخراج شده و با روش RT-PCR، اندازه گیری بیان ژن DNMT3A انجام گرفت.
یافته ها: بیان ژن DNMT3A در بیماران مبتلا به ALL دریافت کننده مرکاپتوپورین به طور معنی دار نسبت به قبل از دریافت دارو بالاتر بود ( 0.05 > P < /span>).
نتیجه گیری: افزایش بیان این ژن در اثر داروی مرکاپتوپرین رخ می دهد. پس احتمالا این دارو از راه فرایندهای اپی ژنتیک ناشی از افزایش متیلاسیون DNA بر سلول های لوسمیک اثر می گذارد.

کلیدواژه‌ها

عنوان مقاله [English]

Altered expression of DNMT3A gene in B-cell acute lymphoblastic leukemia by mercaptopurine

نویسندگان [English]

  • Seyedhossein Hekmatimoghaddam
  • Tahereh Ahmadi
  • Fatemeh Pourrajab
  • Ali Dehghani Firoozabadi
  • Kolan Rahmani

چکیده [English]

Introduction: Current medications used for acute lymphoblastic leukemia (ALL) such as mercaptopurine target molecular factors involved in its onset and progression including DNA methyltransferases (DNMTs) because these enzymes are implicated in methylation and therefore expression of genes which are related to cell proliferation. This study evaluated the effect of mercaptopurine on the DNMT3A gene expression.
Materials and Methods: The study was an analytical study of before and after type, performed on 8 children with B-cell ALL referred to children’s medical center of Tehran enrolled by convenience sampling. Their blood samples were taken in pre-treatment phase as well as 2 months after treatment with mercaptopurine. Ten healthy children referred to Yazd central medical laboratory were also sampled. RNA was extracted from the blood samples, and DNMT3A gene expression was measured by reverse transcriptase polymerase chain reaction (RT-PCR).
Results: DNMT3A gene expression in patients with B-cell ALL who received mercaptopurine was significantly higher compared with pre-treatment time (P < 0.05).
Conclusion: Increased expression of this regulatory gene occurred due to drug mercaptopurine. So, the mechanism of action of this drug may be through epigenetic processes due to higher methylation of DNA in leukemic cells.

کلیدواژه‌ها [English]

  • DNMT3A
  • Epigenesis
  • Gene expression
  • Leukemia
  • lymphoid
  • 6-Mercaptopurine
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مجله علوم پزشکی پارس
دوره 19، شماره 1 - شماره پیاپی 55
فروردین 1400
صفحه 44-53